diff --git a/mypy/checker.py b/mypy/checker.py
index 05a5e91552e0..e24beb31c85e 100644
--- a/mypy/checker.py
+++ b/mypy/checker.py
@@ -2874,6 +2874,39 @@ def remove_optional(typ: Type) -> Type:
         return typ
 
 
+def builtin_item_type(tp: Type) -> Optional[Type]:
+    """Get the item type of a builtin container.
+
+    If 'tp' is not one of the built containers (these includes NamedTuple and TypedDict)
+    or if the container is not parameterized (like List or List[Any])
+    return None. This function is used to narrow optional types in situations like this:
+
+        x: Optional[int]
+        if x in (1, 2, 3):
+            x + 42  # OK
+
+    Note: this is only OK for built-in containers, where we know the behavior
+    of __contains__.
+    """
+    if isinstance(tp, Instance):
+        if tp.type.fullname() in ['builtins.list', 'builtins.tuple', 'builtins.dict',
+                                  'builtins.set', 'builtins.frozenset']:
+            if not tp.args:
+                # TODO: fix tuple in lib-stub/builtins.pyi (it should be generic).
+                return None
+            if not isinstance(tp.args[0], AnyType):
+                return tp.args[0]
+    elif isinstance(tp, TupleType) and all(not isinstance(it, AnyType) for it in tp.items):
+        return UnionType.make_simplified_union(tp.items)  # this type is not externally visible
+    elif isinstance(tp, TypedDictType):
+        # TypedDict always has non-optional string keys.
+        if tp.fallback.type.fullname() == 'typing.Mapping':
+            return tp.fallback.args[0]
+        elif tp.fallback.type.bases[0].type.fullname() == 'typing.Mapping':
+            return tp.fallback.type.bases[0].args[0]
+    return None
+
+
 def and_conditional_maps(m1: TypeMap, m2: TypeMap) -> TypeMap:
     """Calculate what information we can learn from the truth of (e1 and e2)
     in terms of the information that we can learn from the truth of e1 and
@@ -3020,6 +3053,20 @@ def find_isinstance_check(node: Expression,
                     optional_expr = node.operands[1]
                 if is_overlapping_types(optional_type, comp_type):
                     return {optional_expr: remove_optional(optional_type)}, {}
+        elif node.operators in [['in'], ['not in']]:
+            expr = node.operands[0]
+            left_type = type_map[expr]
+            right_type = builtin_item_type(type_map[node.operands[1]])
+            right_ok = right_type and (not is_optional(right_type) and
+                                       (not isinstance(right_type, Instance) or
+                                        right_type.type.fullname() != 'builtins.object'))
+            if (right_type and right_ok and is_optional(left_type) and
+                    literal(expr) == LITERAL_TYPE and not is_literal_none(expr) and
+                    is_overlapping_types(left_type, right_type)):
+                if node.operators == ['in']:
+                    return {expr: remove_optional(left_type)}, {}
+                if node.operators == ['not in']:
+                    return {}, {expr: remove_optional(left_type)}
     elif isinstance(node, RefExpr):
         # Restrict the type of the variable to True-ish/False-ish in the if and else branches
         # respectively
diff --git a/test-data/unit/check-isinstance.test b/test-data/unit/check-isinstance.test
index 8279e1aeafd4..81a1069d8832 100644
--- a/test-data/unit/check-isinstance.test
+++ b/test-data/unit/check-isinstance.test
@@ -1757,7 +1757,6 @@ if isinstance(x, str, 1): # E: Too many arguments for "isinstance"
     reveal_type(x) # E: Revealed type is 'builtins.int'
 [builtins fixtures/isinstancelist.pyi]
 
-
 [case testIsinstanceNarrowAny]
 from typing import Any
 
@@ -1770,3 +1769,209 @@ def narrow_any_to_str_then_reassign_to_int() -> None:
         reveal_type(v)  # E: Revealed type is 'Any'
 
 [builtins fixtures/isinstance.pyi]
+
+[case testNarrowTypeAfterInList]
+# flags: --strict-optional
+from typing import List, Optional
+
+x: List[int]
+y: Optional[int]
+
+if y in x:
+    reveal_type(y)  # E: Revealed type is 'builtins.int'
+else:
+    reveal_type(y)  # E: Revealed type is 'Union[builtins.int, builtins.None]'
+if y not in x:
+    reveal_type(y)  # E: Revealed type is 'Union[builtins.int, builtins.None]'
+else:
+    reveal_type(y)  # E: Revealed type is 'builtins.int'
+[builtins fixtures/list.pyi]
+[out]
+
+[case testNarrowTypeAfterInListOfOptional]
+# flags: --strict-optional
+from typing import List, Optional
+
+x: List[Optional[int]]
+y: Optional[int]
+
+if y not in x:
+    reveal_type(y)  # E: Revealed type is 'Union[builtins.int, builtins.None]'
+else:
+    reveal_type(y)  # E: Revealed type is 'Union[builtins.int, builtins.None]'
+[builtins fixtures/list.pyi]
+[out]
+
+[case testNarrowTypeAfterInListNonOverlapping]
+# flags: --strict-optional
+from typing import List, Optional
+
+x: List[str]
+y: Optional[int]
+
+if y in x:
+    reveal_type(y)  # E: Revealed type is 'Union[builtins.int, builtins.None]'
+else:
+    reveal_type(y)  # E: Revealed type is 'Union[builtins.int, builtins.None]'
+[builtins fixtures/list.pyi]
+[out]
+
+[case testNarrowTypeAfterInListNested]
+# flags: --strict-optional
+from typing import List, Optional, Any
+
+x: Optional[int]
+lst: Optional[List[int]]
+nested_any: List[List[Any]]
+
+if lst in nested_any:
+    reveal_type(lst) # E: Revealed type is 'builtins.list[builtins.int]'
+if x in nested_any:
+    reveal_type(x) # E: Revealed type is 'Union[builtins.int, builtins.None]'
+[builtins fixtures/list.pyi]
+[out]
+
+[case testNarrowTypeAfterInTuple]
+# flags: --strict-optional
+from typing import Optional
+class A: pass
+class B(A): pass
+class C(A): pass
+
+y: Optional[B]
+if y in (B(), C()):
+    reveal_type(y) # E: Revealed type is '__main__.B'
+else:
+    reveal_type(y) # E: Revealed type is 'Union[__main__.B, builtins.None]'
+[builtins fixtures/tuple.pyi]
+[out]
+
+[case testNarrowTypeAfterInNamedTuple]
+# flags: --strict-optional
+from typing import NamedTuple, Optional
+class NT(NamedTuple):
+    x: int
+    y: int
+nt: NT
+
+y: Optional[int]
+if y not in nt:
+    reveal_type(y) # E: Revealed type is 'Union[builtins.int, builtins.None]'
+else:
+    reveal_type(y) # E: Revealed type is 'builtins.int'
+[builtins fixtures/tuple.pyi]
+[out]
+
+[case testNarrowTypeAfterInDict]
+# flags: --strict-optional
+from typing import Dict, Optional
+x: Dict[str, int]
+y: Optional[str]
+
+if y in x:
+    reveal_type(y) # E: Revealed type is 'builtins.str'
+else:
+    reveal_type(y) # E: Revealed type is 'Union[builtins.str, builtins.None]'
+if y not in x:
+    reveal_type(y) # E: Revealed type is 'Union[builtins.str, builtins.None]'
+else:
+    reveal_type(y) # E: Revealed type is 'builtins.str'
+[builtins fixtures/dict.pyi]
+[out]
+
+[case testNarrowTypeAfterInList_python2]
+# flags: --strict-optional
+from typing import List, Optional
+
+x = []  # type: List[int]
+y = None  # type: Optional[int]
+
+# TODO: Fix running tests on Python 2: "Iterator[int]" has no attribute "next"
+if y in x:  # type: ignore
+    reveal_type(y)  # E: Revealed type is 'builtins.int'
+else:
+    reveal_type(y)  # E: Revealed type is 'Union[builtins.int, builtins.None]'
+if y not in x:  # type: ignore
+    reveal_type(y)  # E: Revealed type is 'Union[builtins.int, builtins.None]'
+else:
+    reveal_type(y)  # E: Revealed type is 'builtins.int'
+
+[builtins_py2 fixtures/python2.pyi]
+[out]
+
+[case testNarrowTypeAfterInNoAnyOrObject]
+# flags: --strict-optional
+from typing import Any, List, Optional
+x: List[Any]
+z: List[object]
+
+y: Optional[int]
+if y in x:
+    reveal_type(y) # E: Revealed type is 'Union[builtins.int, builtins.None]'
+else:
+    reveal_type(y) # E: Revealed type is 'Union[builtins.int, builtins.None]'
+
+if y not in z:
+    reveal_type(y) # E: Revealed type is 'Union[builtins.int, builtins.None]'
+else:
+    reveal_type(y) # E: Revealed type is 'Union[builtins.int, builtins.None]'
+[typing fixtures/typing-full.pyi]
+[builtins fixtures/list.pyi]
+[out]
+
+[case testNarrowTypeAfterInUserDefined]
+# flags: --strict-optional
+from typing import Container, Optional
+
+class C(Container[int]):
+    def __contains__(self, item: object) -> bool:
+        return item is 'surprise'
+
+y: Optional[int]
+# We never trust user defined types
+if y in C():
+    reveal_type(y) # E: Revealed type is 'Union[builtins.int, builtins.None]'
+else:
+    reveal_type(y) # E: Revealed type is 'Union[builtins.int, builtins.None]'
+if y not in C():
+    reveal_type(y) # E: Revealed type is 'Union[builtins.int, builtins.None]'
+else:
+    reveal_type(y) # E: Revealed type is 'Union[builtins.int, builtins.None]'
+[typing fixtures/typing-full.pyi]
+[builtins fixtures/list.pyi]
+[out]
+
+[case testNarrowTypeAfterInSet]
+# flags: --strict-optional
+from typing import Optional, Set
+s: Set[str]
+
+y: Optional[str]
+if y in {'a', 'b', 'c'}:
+    reveal_type(y) # E: Revealed type is 'builtins.str'
+else:
+    reveal_type(y) # E: Revealed type is 'Union[builtins.str, builtins.None]'
+if y not in s:
+    reveal_type(y) # E: Revealed type is 'Union[builtins.str, builtins.None]'
+else:
+    reveal_type(y) # E: Revealed type is 'builtins.str'
+[builtins fixtures/set.pyi]
+[out]
+
+[case testNarrowTypeAfterInTypedDict]
+# flags: --strict-optional
+from typing import Optional
+from mypy_extensions import TypedDict
+class TD(TypedDict):
+    a: int
+    b: str
+td: TD
+
+def f() -> None:
+    x: Optional[str]
+    if x not in td:
+        return
+    reveal_type(x) # E: Revealed type is 'builtins.str'
+[typing fixtures/typing-full.pyi]
+[builtins fixtures/dict.pyi]
+[out]
diff --git a/test-data/unit/fixtures/dict.pyi b/test-data/unit/fixtures/dict.pyi
index cf8b61f9397a..d8fc59f60008 100644
--- a/test-data/unit/fixtures/dict.pyi
+++ b/test-data/unit/fixtures/dict.pyi
@@ -19,6 +19,7 @@ class dict(Generic[KT, VT]):
     def __getitem__(self, key: KT) -> VT: pass
     def __setitem__(self, k: KT, v: VT) -> None: pass
     def __iter__(self) -> Iterator[KT]: pass
+    def __contains__(self, item: object) -> bool: pass
     def update(self, a: Mapping[KT, VT]) -> None: pass
     @overload
     def get(self, k: KT) -> Optional[VT]: pass
diff --git a/test-data/unit/fixtures/list.pyi b/test-data/unit/fixtures/list.pyi
index 7b6d1dbd127b..b6e54577fb91 100644
--- a/test-data/unit/fixtures/list.pyi
+++ b/test-data/unit/fixtures/list.pyi
@@ -16,6 +16,7 @@ class list(Generic[T]):
     @overload
     def __init__(self, x: Iterable[T]) -> None: pass
     def __iter__(self) -> Iterator[T]: pass
+    def __contains__(self, item: object) -> bool: pass
     def __add__(self, x: list[T]) -> list[T]: pass
     def __mul__(self, x: int) -> list[T]: pass
     def __getitem__(self, x: int) -> T: pass
diff --git a/test-data/unit/fixtures/python2.pyi b/test-data/unit/fixtures/python2.pyi
index 61e48be4510e..283ba1895a97 100644
--- a/test-data/unit/fixtures/python2.pyi
+++ b/test-data/unit/fixtures/python2.pyi
@@ -11,6 +11,7 @@ class function: pass
 class int: pass
 class str: pass
 class unicode: pass
+class bool: pass
 
 T = TypeVar('T')
 class list(Iterable[T], Generic[T]): pass
diff --git a/test-data/unit/fixtures/set.pyi b/test-data/unit/fixtures/set.pyi
index 79d53e832291..9de7bdaa8096 100644
--- a/test-data/unit/fixtures/set.pyi
+++ b/test-data/unit/fixtures/set.pyi
@@ -13,9 +13,11 @@ class function: pass
 
 class int: pass
 class str: pass
+class bool: pass
 
 class set(Iterable[T], Generic[T]):
     def __iter__(self) -> Iterator[T]: pass
+    def __contains__(self, item: object) -> bool: pass
     def add(self, x: T) -> None: pass
     def discard(self, x: T) -> None: pass
     def update(self, x: Set[T]) -> None: pass
diff --git a/test-data/unit/fixtures/tuple.pyi b/test-data/unit/fixtures/tuple.pyi
index 4e53d12f76e6..e231900cfa20 100644
--- a/test-data/unit/fixtures/tuple.pyi
+++ b/test-data/unit/fixtures/tuple.pyi
@@ -12,6 +12,7 @@ class type:
     def __call__(self, *a) -> object: pass
 class tuple(Sequence[Tco], Generic[Tco]):
     def __iter__(self) -> Iterator[Tco]: pass
+    def __contains__(self, item: object) -> bool: pass
     def __getitem__(self, x: int) -> Tco: pass
     def count(self, obj: Any) -> int: pass
 class function: pass
diff --git a/test-data/unit/fixtures/typing-full.pyi b/test-data/unit/fixtures/typing-full.pyi
index 62fac70034c0..fb6b1d3e596d 100644
--- a/test-data/unit/fixtures/typing-full.pyi
+++ b/test-data/unit/fixtures/typing-full.pyi
@@ -126,6 +126,7 @@ class Mapping(Iterable[T], Protocol[T, T_co]):
     def get(self, k: T, default: Union[T_co, V]) -> Union[T_co, V]: pass
     def values(self) -> Iterable[T_co]: pass  # Approximate return type
     def __len__(self) -> int: ...
+    def __contains__(self, arg: object) -> int: pass
 
 @runtime
 class MutableMapping(Mapping[T, U], Protocol):