An antiserum to human melanoma has been produced in a chimpanzee by hyperimmunization with melanoma cells from a single donor. After absorption with the peripheral blood lymphocytes of the tumor donor, this antiserum is specifically cytotoxic to melanoma cells from 14 tissue culture cell lines and to cells from 8 fetal fibroblast cell lines. Peripheral blood lymphocytes-absorbed antiserum is negative when tested against a large panel of normal peripheral blood lymphocytes and fibroblasts and against eight non-melanoma neoplastic tissue culture cell lines. Subsequent absorption with melanoma cells from any of seven sources removes all antimelonoma and all antifetal reactivity of the antiserum. Similar absorption with fetal cells removes all antifetal activity but does not completely remove the antimelanoma activity. The immunoglobulin G fraction of the antiserum is shown to possess the cytotoxic activity.