Antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by human peripheral blood mononuclear cells (85 % lymphocytes and 15 % monocytes) or lymphocyte-enriched (98 % lymphocytes) effector cells against human red blood cell (HRBC) targets of various Rh genotypes, with or without papain treatment, was tested in an 18-hour ⁵¹Cr release assay. The HRBC were sensitized with Rh₀GAM, an anti-Rh₀ (D) IgG fraction. Mononuclear cell effectors were found to lyse papain treated Rh₀ (D) homozygous cells to a greater degree than Rh₀ (D) heterozygotes. The genotypes of the HRBC targets, in order of the amount of lysis from highest to lowest was R₁R₁, R₂R₂ or R₁R₂, R₂ r, R₁r, R₀r, rr. When the target cells were not papain treated and mononuclear cell effectors were used, the amount of lysis was low and the % specific lysis for Rh₀ (D) homozygote and heterozygote HRBC was equivalent. Lymphocyteenriched effector cells did not lyse the homozygous target cells to a greater degree than the heterozygotes, although the amount of lysis for both types of HRBC was greater than that noted using mononuclear cells as effectors.