Three lymphocyte clones, derived by micromanipulation from peripheral blood lymphocytes (PBL) of a melanoma patient and expressing a broad pattern of reactivity against different target cells, were analyzed for the involvement of T-cell markers and HLA antigens in the lysis of target cells by blocking experiments with a panel of monoclonal antibodies (MAbs). The clones lysed autologous melanoma cells (Me 28) and 18 out of 22 allogeneic targets including neoplastic and normal cells of different histological origin. Anti-T3 and anti-T8 MAbs strongly inhibited the cytotoxicity of the lymphocyte clones against Me 28, 3 allogeneic melanomas and 3 carcinomas, but failed to affect the lysis of K562. Anti-HLA class-I MAb (w6/32) produced a significant enhancement of the lysis of Me 28 by the 3 clones without modifying cytotoxicity against one allogeneic melanoma or against K562 cells. Anti-HLA class-II MAb (D1.12) did not affect the lysis of the same targets by the 3 clones. These results thus indicate that some anti-melanoma CTL clones may interact with autologous tumor cells by the T3 and T8 structures in an HLA class-I unrestricted manner.