Human epidermal cells dissociated by repeated trypsinization of skin explants were stimulatory to allogeneic lymphocytes in mixed lymphocyte skin-cell cultures. After elimination of the lymphocytes proliferating in response to a particular allogeneic lymphocyte donor by a "hot" pulse of 3H-thymidine of high specific activity, the viable lymphocytes remaining in culture were still capable of responding to stimulation by epidermal cells from the same donor. The response towards allogeneic epidermal cells could only partially be eliminated by 3H-thymidine treatment. This treatment, however, also partially eliminated the secondary stimulation response towards lymphocytes from the epidermal cell donor used initially, but did not alter the response to lymphoid or epidermal cells from an unrelated third party donor. In addition, HL-A antisera, which specifically inhibited the stimulatory capacity of mitomycin-treated lymphocytes that carried the relevant HL-A antigen also inhibited the stimulatory properties of epidermal cells from the same donor.