The overall objective was to develop a simple and objective in vitro cell-mediated cytotoxic test with (skin) epidermal cells as targets. The plan was to develop the test initially with mouse cells because of the ready availability of uniform, genetically defined (inbred) strains and some "leads" in the literature where mouse epidermal cells were used as targets for antibody and complement mediated cytotoxicity. Later, the extension to other species, including man, would be explored. The specific objective was to adapt the rapid chromium-release assay of Canty and Wunderlich for use in microtiter trays with freshly explanted and short-term cultured epidermal cells as Cr51-labeled targets for allogeneic immune lymphoid cells. Having demonstrated the feasibility of the model, attention will now be focused on using it to study reactions to the Sk histocompatibility antigen. Mouse radiation chimeras will be produced which are immunologically tolerant to allogeneic lymphoid cells, but which vigorously reject skin allografts from the same donor strain. The cytotoxic response of the hosts' lymphoid cells to donor epidermal and lymphoid cells will then be assayed in vitro. In addition, the possibility of using the model to assay the response to tumor specific antigens in chemically-induced mouse skin carcinoma will be explored.