Keratin proteins synthesized by dorsal or tarsometatarsal embryonic chick epidermis in heterotopic and heterospecific epidermal-dermal recombinants were analyzed by polyacrylamide gel electrophoresis and were compared to those produced by normal nondissociated dorsal and tarsometatarsal embryonic skin, as well as to those produced by control homotopic recombinants. Recombinant skins were grafted on the chick chorioallantoic membrane and grown for 8 or 11 days. Recombinants comprising dorsal feather-forming dermis formed feathers, irrespective of the origin of the epidermis. The electrophoretic band patterns of the keratins extracted from these feathers were of typical feather type. Conversely recombinants comprising tarsometatarsal scale-forming dermis formed scales, irrespective of the origin of the epidermis. The band patterns of the keratins extracted from the epidermis of these scales were of typical scale type. Heterospecific recombinants comprising chick dorsal feather-forming epidermis and mouse plantar dermis gave rise to six footpads arranged in a typical mouse pattern. In these recombinants, the chick epidermis produced keratins, the band pattern of which was of typical chick scale type. These results demonstrate that the dermis not only induces the formation of cutaneous appendages in confirmity with its regional origin, but also triggers off in the epidermis the biosynthesis of either of two different keratin types, in accordance with the regional type (feather, scale, or pad) of cutaneous appendages induced. The possible relationship between region-specific morphogenesis and cytodifferentiation is discussed in comparison with results obtained in other kinds of epithelial-mesenchymal interactions.