Integra artificial skin is an effective means of treatment for full-thickness burns. In extensive burn injury the use of such skin substitutes may become the treatment of choice. The artificial skin consists of a dermal substitute of bovine collagen and chondroitin-6-sulfate and an epidermal layer of synthetic polysiloxane polymer (Silastic). Serial biopsy specimens were obtained from 131 patients during a period of 7 days to 2 years after application. In this histologic study, six sequential phases of repair were discerned. In addition, there were occasional unusual histologic features, eosinophilic infiltration, and/or macrophage-derived giant cell formation in the wound area; however, such findings did not clinically correlate with a negative response to Integra artificial skin. Good repair was obtained, with rare exceptions. An intact dermis was achieved as well as definitive closure of a complete epidermal layer with a minimum of scarring.