Although xenografts can be rejected by humoral or cellular mechanisms, the relative contribution of each remains unknown for any given recipient-donor combination. Moreover, the cells involved in cell-mediated events, as well as the mechanisms by which these cells recognize xenoantigens, remain controversial. It would be advantageous to have a model in which either, as well as various parts of either, could be investigated in the absence of the other, as well as in the absence of events taking place during organ engraftment. In the present report, rejection of rat skin xenografts was monitored after adoptive transfer of unique populations of highly purified lymphoid cells to previously transplanted immunodeficient C.B17 Scid/Scid mice. Purified T cells and, unexpectedly, purified CD4+ T cells alone and purified CD8+ T cells alone rejected rat xenografts. Alternatives that may explain these findings are discussed.