Four monoclonal antibodies to human melanoma-associated antigens (MAA) were found to be able to mediate specific cell-dependent lysis (ADCC) of cultured human melanoma cells. The extent of specific lysis of melanoma cells was influenced by the effector to target cell ratio, the amount of antibody added to the reaction mixture, and the incubation time. Cultured melanoma cells treated for 16 h with puromycin or cycloheximide (final concentration, 1.0 micrograms/ml) displayed increased susceptibility to ADCC even though the cell surface expression of MAA was not changed. On the other hand, treatment of melanoma cells with tunicamycin (final concentration, 1.0 microgram/ml) reduced the expression of MAA but did not affect susceptibility to ADCC. These findings suggest that other properties of the target cell membrane besides antigen density play a role in the outcome of ADCC reaction.