When peripheral blood lymphocytes and human red cells coated with IgG were incubated in vitro in culture medium, antibody-dependent lymphocyte-mediated lysis was observed. This lysis was markedly inhibited by the addition of purified monoclonal IgG1 (1000 microgram/ml) to the culture medium. In contrast, lysis by lymphocytes of sensitized red cells in the presence of undiluted human serum was equal to or greater than lysis in medium alone, even in the presence of IgG1 at 1000 microgram/ml, despite the high concentration of IgG in human serum (6000--19,000 microgram/ml). Serum heated to 56 degrees C for 30 min also restored lysis in the presence of IgG1. When serum was separated into three fractions by passage through a Sephadex G-200 column, the third fraction, which contained proteins with a molecular weight of less than 100,000 d (but neither of the other two fractions nor purified human albumin), restored lymphocyte-mediated lysis in the presence of IgG1.