The high morbidity and mortality from extensive burns are due mainly to bacterial invasion. This can be prevented by early closure of the burn wounds with autologous skin grafts. In patients with burns of large area, this strategy cannot be fully realized because of the lack of adequate donor sites for grafting. We have demonstrated that it is possible (1) to take a small sample of full thickness epidermis from a badly burned patient and grow the cells in culture using methods we have worked out over the past 10 years, so as to obtain enough cultured epithelium to cover the entire body surface. (2) To prepare the cultured epithelium in a form suitable for grafting. (3) To apply such grafts to humans under clinical conditions, and obtain high frequency of take. (4) To regenerate by this method epidermis covering over 50% of body surface and possessing good quality over moderate to long term. We propose to advance the basic and applied aspects of this system in order to provide living autologous epidermal coverage for any kind of epidermal defect in the human. This procedure is to be evaluated as a definitive solution to the problem of covering in burns of large area. The research will cover short and long term study of the quality of the epidermis regenerated, optimization of the methods of preparing, applying and caring for the grafts and some basic studies relevant to the proliferative potential of the epidermal keratinocyte and its terminal differentiation.