diff --git a/src/librustc/middle/infer/combine.rs b/src/librustc/middle/infer/combine.rs
index e286855c28548..8b29ef9b8800f 100644
--- a/src/librustc/middle/infer/combine.rs
+++ b/src/librustc/middle/infer/combine.rs
@@ -263,7 +263,13 @@ pub trait Combine<'tcx> : Sized {
             Err(ty::terr_projection_name_mismatched(
                 expected_found(self, a.item_name, b.item_name)))
         } else {
-            let trait_ref = try!(self.trait_refs(&*a.trait_ref, &*b.trait_ref));
+            // Note that the trait refs for the projection must be
+            // *equal*. This is because there is no inherent
+            // relationship between `<T as Foo>::Bar` and `<U as
+            // Foo>::Bar` that we can derive based on how `T` relates
+            // to `U`. Issue #21726 contains further discussion and
+            // in-depth examples.
+            let trait_ref = try!(self.equate().trait_refs(&*a.trait_ref, &*b.trait_ref));
             Ok(ty::ProjectionTy { trait_ref: Rc::new(trait_ref), item_name: a.item_name })
         }
     }
diff --git a/src/librustc_typeck/variance.rs b/src/librustc_typeck/variance.rs
index dd42c66795651..6c5950e4df5ba 100644
--- a/src/librustc_typeck/variance.rs
+++ b/src/librustc_typeck/variance.rs
@@ -793,7 +793,7 @@ impl<'a, 'tcx> ConstraintContext<'a, 'tcx> {
                     trait_def.generics.types.as_slice(),
                     trait_def.generics.regions.as_slice(),
                     trait_ref.substs,
-                    variance);
+                    self.invariant);
             }
 
             ty::ty_trait(ref data) => {
diff --git a/src/test/compile-fail/associated-types-subtyping-1.rs b/src/test/compile-fail/associated-types-subtyping-1.rs
new file mode 100644
index 0000000000000..f9106ba3960b1
--- /dev/null
+++ b/src/test/compile-fail/associated-types-subtyping-1.rs
@@ -0,0 +1,55 @@
+// Copyright 2015 The Rust Project Developers. See the COPYRIGHT
+// file at the top-level directory of this distribution and at
+// http://rust-lang.org/COPYRIGHT.
+//
+// Licensed under the Apache License, Version 2.0 <LICENSE-APACHE or
+// http://www.apache.org/licenses/LICENSE-2.0> or the MIT license
+// <LICENSE-MIT or http://opensource.org/licenses/MIT>, at your
+// option. This file may not be copied, modified, or distributed
+// except according to those terms.
+
+#![allow(unused_variables)]
+
+trait Trait<'a> {
+    type Type;
+
+    fn method(&'a self) { }
+}
+
+fn method1<'a,'b,T>(x: &'a T, y: &'b T)
+    where T : for<'z> Trait<'z>, 'a : 'b
+{
+    // Note that &'static T <: &'a T.
+    let a: <T as Trait<'a>>::Type = loop { };
+    let b: <T as Trait<'b>>::Type = loop { };
+    let _: <T as Trait<'a>>::Type = a;
+}
+
+fn method2<'a,'b,T>(x: &'a T, y: &'b T)
+    where T : for<'z> Trait<'z>, 'a : 'b
+{
+    // Note that &'static T <: &'a T.
+    let a: <T as Trait<'a>>::Type = loop { };
+    let b: <T as Trait<'b>>::Type = loop { };
+    let _: <T as Trait<'b>>::Type = a; //~ ERROR mismatched types
+}
+
+fn method3<'a,'b,T>(x: &'a T, y: &'b T)
+    where T : for<'z> Trait<'z>, 'a : 'b
+{
+    // Note that &'static T <: &'a T.
+    let a: <T as Trait<'a>>::Type = loop { };
+    let b: <T as Trait<'b>>::Type = loop { };
+    let _: <T as Trait<'a>>::Type = b; //~ ERROR mismatched types
+}
+
+fn method4<'a,'b,T>(x: &'a T, y: &'b T)
+    where T : for<'z> Trait<'z>, 'a : 'b
+{
+    // Note that &'static T <: &'a T.
+    let a: <T as Trait<'a>>::Type = loop { };
+    let b: <T as Trait<'b>>::Type = loop { };
+    let _: <T as Trait<'b>>::Type = b;
+}
+
+fn main() { }
diff --git a/src/test/compile-fail/variance-associated-types.rs b/src/test/compile-fail/variance-associated-types.rs
new file mode 100644
index 0000000000000..ecb2287769bbd
--- /dev/null
+++ b/src/test/compile-fail/variance-associated-types.rs
@@ -0,0 +1,30 @@
+// Copyright 2015 The Rust Project Developers. See the COPYRIGHT
+// file at the top-level directory of this distribution and at
+// http://rust-lang.org/COPYRIGHT.
+//
+// Licensed under the Apache License, Version 2.0 <LICENSE-APACHE or
+// http://www.apache.org/licenses/LICENSE-2.0> or the MIT license
+// <LICENSE-MIT or http://opensource.org/licenses/MIT>, at your
+// option. This file may not be copied, modified, or distributed
+// except according to those terms.
+
+// Test that the variance computation considers types/regions that
+// appear in projections to be invariant.
+
+trait Trait<'a> {
+    type Type;
+
+    fn method(&'a self) { }
+}
+
+#[rustc_variance]
+struct Foo<'a, T : Trait<'a>> { //~ ERROR ItemVariances(types=[[+];[];[]], regions=[[-];[];[]])
+    field: (T, &'a ())
+}
+
+#[rustc_variance]
+struct Bar<'a, T : Trait<'a>> { //~ ERROR ItemVariances(types=[[o];[];[]], regions=[[o];[];[]])
+    field: <T as Trait<'a>>::Type
+}
+
+fn main() { }
diff --git a/src/test/run-pass/issue-21726.rs b/src/test/run-pass/issue-21726.rs
new file mode 100644
index 0000000000000..09d1a3bca6901
--- /dev/null
+++ b/src/test/run-pass/issue-21726.rs
@@ -0,0 +1,44 @@
+// Copyright 2015 The Rust Project Developers. See the COPYRIGHT
+// file at the top-level directory of this distribution and at
+// http://rust-lang.org/COPYRIGHT.
+//
+// Licensed under the Apache License, Version 2.0 <LICENSE-APACHE or
+// http://www.apache.org/licenses/LICENSE-2.0> or the MIT license
+// <LICENSE-MIT or http://opensource.org/licenses/MIT>, at your
+// option. This file may not be copied, modified, or distributed
+// except according to those terms.
+
+// Regression test for #21726: an issue arose around the rules for
+// subtyping of projection types that resulted in an unconstrained
+// region, yielding region inference failures.
+
+fn main() { }
+
+fn foo<'a>(s: &'a str) {
+    let b: B<()> = B::new(s, ());
+    b.get_short();
+}
+
+trait IntoRef<'a> {
+    type T: Clone;
+    fn into_ref(self, &'a str) -> Self::T;
+}
+
+impl<'a> IntoRef<'a> for () {
+    type T = &'a str;
+    fn into_ref(self, s: &'a str) -> &'a str {
+        s
+    }
+}
+
+struct B<'a, P: IntoRef<'a>>(P::T);
+
+impl<'a, P: IntoRef<'a>> B<'a, P> {
+    fn new(s: &'a str, i: P) -> B<'a, P> {
+        B(i.into_ref(s))
+    }
+
+    fn get_short(&self) -> P::T {
+        self.0.clone()
+    }
+}