Deuterium labeling has been shown previously to affect thermodynamic interactions at polymer surfaces, polymer/polymer heterogeneous interfaces, and in bulk ( away from a surface or interface). However, the changes in polymer-polymer interactions due to deuterium labeling have not been thoroughly investigated for highly immiscible systems. It is shown here that deuterium labeling can influence polymer-polymer interactions at heterogeneous interfaces with highly immiscible systems, namely, polystyrene/poly(2-vinylpyridine) (PS/P2VP), polystyrene/ poly(4-vinylpyridine) (PS/P4VP), and polystyrene/ poly( methyl methacrylate) (PS/PMMA). Using secondary ion mass spectrometry, segregation of deuterium labeled polystyrene (dPS) in a dPS + unlabeled PS ( dPS: hPS) blend layer was observed at the dPS: hPS/hP2VP, dPS: hPS/hP4VP, and dPS: hPS/hPMMA heterogeneous interfaces. However, a reference system involving PS on a PS brush shows no segregation of dPS to the interface.