ExtractAntibody-dependent cell-mediated cytotoxicity (ADCMC) was measured in a51Cr-release assay with antibody-sensitized human red blood cells (RBC) as target cells and nonimmune isologous or autologous mononuclear peripheral blood leukocytes (MPBL) as effector cells. ADCMC was readily demonstrable within 6 hr and was independent of exogenous complement (C'). The specificity of the ADCMC reaction was determined by the antiserum employed. Anti-A, anti-B, anti-D, and anti-c sera were all active in ADCMC; the specific lysis was between 35 and 50% with antiserum dilution of 1/1,000, using 105target cells and 106MPBL. Anti-C, anti-E, and anti-e sera had no detectable activity. Sephadex column separation suggested that this activity was by antibodies of the IgG class.Cord RBC from infants with RhD fetal-maternal incompatibility were lysed by autologous or isologous MPBL in the absence of exogenous antiserum. ADCMC was between 22% and 42% incases with high direct Coombs' test, but was negative with low direct Coombs' test as in five cases of ABO incompatibility.SpeculationIn hemolytic disease of the newborn, the precise mechanisms involved in the destruction of fetal erythrocytes sensitized with maternal antibodies are not well known. The experiments described in this report raise the possibility that ADCMC could be operativein vivo