An assay for antibody-dependent cell-mediated cytotoxicity which uses whole blood as effector and autologous lymphocytes sensitized with rabbit anti-human lymphocyte serum as targets is assessed. Comparison with performances of purified lymphocytes shows that whole blood yields approximately the same cytotoxicity levels as the lymphocytes which can be separated from the corresponding volume of blood. This equivalence is not seen at the early stage of cytolysis, whole blood reaching its plateau stage 1 h later. A contribution of phagocytic cells to lysis of the target cells is ruled out. The presence of plasma does not modify the cytolytic capacity of the blood of healthy subjects. The test may be performed with less than 1 ml of blood and is suitable for repeated evaluation of the immunologic status of patients, for evaluation of plasma factors in diseases and of the effects of agents inducing lymphocyte redistribution.