Peripheral blood lymphocytes (PBLs) are not normally susceptible to killing by autologous natural killer (NK) cells. Treatment of human PBLs with neuraminidase removes terminal sialic acid residues and renders them susceptible to cytotoxicity by autologous NK cells. This neuraminidase-induced natural killing can be inhibited with cold targets such as K-562, and also by human red blood cells of blood group A. In addition NK cells will kill certain allogeneic PBLs even when they are fully sialylated, and this killing appears to be directed against the carbohydrate ABO blood group of the foreign target. For example group O NK cells will kill untreated group A PBLs, and this cytotoxicity can be inhibited by red blood cells of group A, but not of group O. The implications of this finding for NK cell recognition of targets are discussed.