diff --git a/mypy/semanal.py b/mypy/semanal.py
index 95a7bf6e3630..a29da6aabdac 100644
--- a/mypy/semanal.py
+++ b/mypy/semanal.py
@@ -758,8 +758,12 @@ def clean_up_bases_and_infer_type_variables(self, defn: ClassDef) -> None:
         Now we will remove Generic[T] from bases of Foo and infer that the
         type variable 'T' is a type argument of Foo.
 
+        We also process six.with_metaclass() here.
+
         Note that this is performed *before* semantic analysis.
         """
+        # First process six.with_metaclass if present and well-formed
+        defn.base_type_exprs, defn.metaclass = self.check_with_metaclass(defn)
         removed = []  # type: List[int]
         declared_tvars = []  # type: TypeVarList
         for i, base_expr in enumerate(defn.base_type_exprs):
@@ -938,6 +942,7 @@ def analyze_base_classes(self, defn: ClassDef) -> None:
 
         base_types = []  # type: List[Instance]
         info = defn.info
+
         for base_expr in defn.base_type_exprs:
             try:
                 base = self.expr_to_analyzed_type(base_expr)
@@ -989,6 +994,27 @@ def analyze_base_classes(self, defn: ClassDef) -> None:
         if defn.info.is_enum and defn.type_vars:
             self.fail("Enum class cannot be generic", defn)
 
+    def check_with_metaclass(self, defn: ClassDef) -> Tuple[List[Expression], Optional[str]]:
+        # Special-case six.with_metaclass(M, B1, B2, ...).
+        base_type_exprs, metaclass = defn.base_type_exprs, defn.metaclass
+        if metaclass is None and len(base_type_exprs) == 1:
+            base_expr = base_type_exprs[0]
+            if isinstance(base_expr, CallExpr) and isinstance(base_expr.callee, RefExpr):
+                base_expr.callee.accept(self)
+                if (base_expr.callee.fullname == 'six.with_metaclass'
+                        and len(base_expr.args) >= 1
+                        and all(kind == ARG_POS for kind in base_expr.arg_kinds)):
+                    metaclass_expr = base_expr.args[0]
+                    if isinstance(metaclass_expr, NameExpr):
+                        metaclass = metaclass_expr.name
+                    elif isinstance(metaclass_expr, MemberExpr):
+                        metaclass = get_member_expr_fullname(metaclass_expr)
+                    else:
+                        self.fail("Dynamic metaclass not supported for '%s'" % defn.name,
+                                  metaclass_expr)
+                    return (base_expr.args[1:], metaclass)
+        return (base_type_exprs, metaclass)
+
     def expr_to_analyzed_type(self, expr: Expression) -> Type:
         if isinstance(expr, CallExpr):
             expr.accept(self)
diff --git a/test-data/unit/check-classes.test b/test-data/unit/check-classes.test
index 1dd3353ec903..d6f011719d53 100644
--- a/test-data/unit/check-classes.test
+++ b/test-data/unit/check-classes.test
@@ -3137,3 +3137,94 @@ class M(type):
 class A(metaclass=M): pass
 reveal_type(type(A).x)  # E: Revealed type is 'builtins.int'
 
+[case testSixWithMetaclass]
+import six
+class M(type):
+    x = 5
+class A(six.with_metaclass(M)): pass
+reveal_type(type(A).x)  # E: Revealed type is 'builtins.int'
+
+[case testSixWithMetaclass_python2]
+import six
+class M(type):
+    x = 5
+class A(six.with_metaclass(M)): pass
+reveal_type(type(A).x)  # E: Revealed type is 'builtins.int'
+
+[case testFromSixWithMetaclass]
+from six import with_metaclass
+class M(type):
+    x = 5
+class A(with_metaclass(M)): pass
+reveal_type(type(A).x)  # E: Revealed type is 'builtins.int'
+
+[case testSixWithMetaclassImportFrom]
+import six
+from metadefs import M
+class A(six.with_metaclass(M)): pass
+reveal_type(type(A).x)  # E: Revealed type is 'builtins.int'
+[file metadefs.py]
+class M(type):
+    x = 5
+
+[case testSixWithMetaclassImport]
+import six
+import metadefs
+class A(six.with_metaclass(metadefs.M)): pass
+reveal_type(type(A).x)  # E: Revealed type is 'builtins.int'
+[file metadefs.py]
+class M(type):
+    x = 5
+
+[case testSixWithMetaclassAndBase]
+import six
+class M(type):
+    x = 5
+class A:
+    def foo(self): pass
+class B:
+    def bar(self): pass
+class C1(six.with_metaclass(M, A)): pass
+class C2(six.with_metaclass(M, A, B)): pass
+reveal_type(type(C1).x)  # E: Revealed type is 'builtins.int'
+reveal_type(type(C2).x)  # E: Revealed type is 'builtins.int'
+C1().foo()
+C1().bar()  # E: "C1" has no attribute "bar"
+C2().foo()
+C2().bar()
+C2().baz()  # E: "C2" has no attribute "baz"
+
+[case testSixWithMetaclassGenerics]
+from typing import Generic, GenericMeta, TypeVar
+import six
+class DestroyableMeta(type):
+    pass
+class Destroyable(six.with_metaclass(DestroyableMeta)):
+    pass
+T_co = TypeVar('T_co', bound='Destroyable', covariant=True)
+class ArcMeta(GenericMeta, DestroyableMeta):
+    pass
+class Arc(six.with_metaclass(ArcMeta, Generic[T_co], Destroyable)):
+    pass
+class MyDestr(Destroyable):
+    pass
+reveal_type(Arc[MyDestr]())  # E: Revealed type is '__main__.Arc[__main__.MyDestr*]'
+[builtins fixtures/bool.pyi]
+
+[case testSixWithMetaclassErrors]
+import six
+class M(type): pass
+class A(object): pass
+def f() -> type: return M
+class C1(six.with_metaclass(M), object): pass  # E: Invalid base class
+class C2(C1, six.with_metaclass(M)): pass  # E: Invalid base class
+class C3(six.with_metaclass(A)): pass  # E: Metaclasses not inheriting from 'type' are not supported
+class C4(six.with_metaclass(M), metaclass=M): pass  # E: Invalid base class
+class C5(six.with_metaclass(f())): pass  # E: Dynamic metaclass not supported for 'C5'
+
+[case testSixWithMetaclassErrors_python2-skip]
+# No error here yet
+import six
+class M(type): pass
+class C4(six.with_metaclass(M)):
+    __metaclass__ = M
diff --git a/test-data/unit/lib-stub/six.pyi b/test-data/unit/lib-stub/six.pyi
new file mode 100644
index 000000000000..a6faa32988cb
--- /dev/null
+++ b/test-data/unit/lib-stub/six.pyi
@@ -0,0 +1,2 @@
+from typing import Type
+def with_metaclass(mcls: Type[type], *args: type) -> type: pass
diff --git a/test-data/unit/lib-stub/typing.pyi b/test-data/unit/lib-stub/typing.pyi
index 01ac7b14f7b9..51ffcca74fac 100644
--- a/test-data/unit/lib-stub/typing.pyi
+++ b/test-data/unit/lib-stub/typing.pyi
@@ -3,6 +3,8 @@
 
 from abc import abstractmethod
 
+class GenericMeta(type): pass
+
 cast = 0
 overload = 0
 Any = 0