From sera of parous women, we selected 100 samples that lacked cytotoxic antibodies to human peripheral lymphocytes from at least 80 unrelated persons. These sera were then reacted with a panel of 17 cultured human lymphoid cells in the complement-dependent cytotoxic 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: in fact, 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. It is suggested that antigens detected by this approach may be similar to the Ia antigens of the mouse.