Microcytotoxicity tests were used to study complement-dependent cytotoxicity of 2 monoclonal IgG2a antibodies, 96.5 and 118.1, both alone and in combination. These antibodies are specific for 2 antigenic determinants, p97a and p97b, respectively, of p97, a cell-surface glycoprotein present on most human melanomas and, in smaller amounts, on other tumors and normal tissues. For 10 of 12 melanoma lines, complement-dependent cytotoxicity was much greater in the presence of both antibodies than with either antibody alone. Synergism was not observed when the antibodies were tested in combination with an IgG2a antibody to a different cell-surface glycoprotein, nor was it detected in tests of 4 non-melanoma cell lines.