Intact cultures of pure epidermal cells, MATERIALS AND METHODS derived as single cell suspensions from perinatal C3H mouse skin, were grafted back onto syngeneic recipients. The cells were grown on collagen gels that formed the bottom of special silicon chambers. The graft bed was a capsule of granulation tissue formed around a glass disc implanted between the back skin and thoracic wall of C3H mice and left in place for 3–4 weeks. Chambers with 1- to 4-day-old epidermal cultures growing as intact cell layers on the collagen were implanted into the capsules after the glass discs were removed. During observation of up to 8 weeks, the implanted cells formed an intact, well-differentiated epidermis in 45 of 47 animals that had retained their chambers among a group of 61 mice grafted initially. Control mice receiving chambers with only collagen and medium never formed new epidermis. The results demonstrated that disintegrated and cultivated epidermal cells could resume normal functioning in vivo, forming a wellorganized epidermis on the artificial graft bed. This experimental technique seems particularly suited for investigation of the function of the epidermis in skin allograft rejection and chemical carcinogenesis in cultured epidermal cells.