From sera of parous women, 100 samples that lacked cytotoxic antibodies to human peripheral lymphocytes were selected from at least 80 unrelated persons. These sera were then reacted with a panel of 17 cultured human lymphoid cells in the complement-dependent cytotoxicity test. Forty-six sera contained cytotoxic antibodies apparently directed to an antigenic system distinct from HL-A antigens and other known cell surface markers. Rabbit serum was the most efficient source of complement with these cytotoxic antibodies, which did not appear to be directed to tumor associated antigens; no lysis of melanoma cells or leukemic cells could be detected. Ten specificities could be identified which were represented on the cultured human lymphoid cells in various combinations. Antigens detected by this approach may be similar to the Ia [immune response associated] antigens of the mouse.