We derived from blood lymphocytes of a melanoma patient a large number of cytolytic T-cell clones directed against a cell line of the autologous tumor. Three distinct groups of antigens were recognized by these CTL on the autologous melanoma cells: group A consisted of stable antigens present on all sublines, whereas antigens B and C appeared unstable and were expressed by distinct sublines. In vitro immunoselections with various anti-A CTL clones were applied to the melanoma cells and variants resistant to 3 different CTL clones were obtained. These variants remained sensitive to other anti-A CTL clones, indicating that group A comprises at least 4 different antigens (D, E, F and A'). From a total of 76 CTL clones obtained from lymphocytes collected from the patient at various times, we found that 45 were anti-B, 17 were anti-C, 2 were anti-D, 9 were anti-E, 2 were anti-F and I was anti-A'. It is therefore likely that the 6 antigens identified by these CTL clones represent all or nearly all the transplantation antigens recognized by autologous CTL on this human melanoma.