The dermal influence on the epidermis during scale formation in reptiles is poorly known. Cells of the superficial dermis are not homogeneously distributed beneath the epidermis, but are instead connected to specific areas of the epidermis. Dermal cells are joined temporarily or cyclically through the basement membrane, with the reactive region of the epidermis forming specific regions of dermo-epidermal interactions. In these regions morphoregulatory molecules may be exchanged between the dermis and the connected epidermis. Possible changes in the localization of these regions in the skin may result in the production of different appendages, in accordance with the genetic makeup of the epidermis in each species. Regions of dermo-epidermal interactions seem to move their position during development. A hypothesis on the development and evolution of scales, hairs, and feathers from sarcopterigian fish to amniotes is presented, based on the different localization and extension of regions of dermo-epidermal interactions in the skin. It is hypothesized that, during phylogenesis, possible variations in the localization and extension of these regions, from the large scales of basic amniotes to those of sauropsid amniotes, may have originated scales with hard (beta)-keratin. In extant reptiles, extended regions of dermo-epidermal interaction form most of the expanse of outer scale surface. It is hypothesized that the reduction of large regions of dermo-epidermal interactions into small areas in the skin were the origin of dermal condensations. In mammals, small regions of dermo-epidermal interactions have invaginated, forming the dermal papilla with the associated hair matrix epidermis. In birds, small regions of dermo-epidermal interactions have reduced the original scale surface of archosaurian scales, forming the dermal papilla. The latter has invaginated in association with the collar epidermis from which feathers were produced. J. Exp. Zool. (Mol. Dev. Evol.) 302B:365–383, 2004. © 2004 Wiley-Liss, Inc.