The feasibility of utilizing neonatal human foreskins grafted to congenitally athymic nude mice for carcinogenesis studies was explored. Human grafts could be maintained morphologically intact for at least as long as 27 weeks. Topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) induced hyperplasia in human skin. Systemic administration of urethane followed by twice weekly topical TPA applications induced no mouse skin tumors in ungrafted nude mice and a moderate number in grafted nude mice. Two benign squamous papillary lesions developed in the human graft sites receiving TPA. One of these was likely of human origin but definitive origin of the second was uncertain.