Cultured epithelial autografts transplanted to homograft dermis were analyzed histopathologically from 9 days to 2.25 years after grafting and compared with cultured epithelial autografts transplanted to wound beds devoid of homograft dermis in the same patient. The results suggested that grafting to a dermal substrate accelerates biologic events in skin regeneration from cultured epithelial autografts. Both rete ridge development and normalization of the epidermal keratin program from a “hyperproliferative” to a normal pattern occurred months sooner in the cultured epithelial autografts placed on a dermal matrix. Regeneration of anchoring fibrils was also accelerated. Neither repopulation by Langerhans cells nor repigmentation appeared to be altered significantly by grafting to dermal tissue. By special stain, the elastin network of the allograft dermis could still be visualized at 2.25 years, indicating long-term persistence of the homograft matrix. By clinical assessment the rate of successful engraftment (“take rate”) of cultured epithelial autografts grafted to allodermis was estimated to be about 95%, and long-term durability was excellent.