Although it is widely accepted that T cells have a major role in specific tumour immunity, there is now much evidence that natural killer (NK) cells, which exist in many species and spontaneously lyse certain tumour cells in vitro, provide early resistance against tumour growth. Human NK-cell activity can be augmented in vitro by interferon and its inducers, including polyinosinic:polycytidylic acid (poly I:C); furthermore, NK-like activity is generated in mixed leukocyte cultures (MLCs) as is specific cytotoxic T-cell (Tc) activity. When effector cells generated in human MLCs lyse allogeneic or autologous virus-transformed or tumour cells, it has been difficult to evaluate the relative contributions of Tc and NK-like cells to the lysis because the latter, like T cells, can form rosettes with sheep erythrocytes and react with xenogeneic anti-human thymocyte serum. We report here that monoclonal antibodies against human mononuclear cell subpopulations can distinguish Tc from NK and NK-like cells. OKT3 or OKT8 monoclonal antibodies (reactive with virtually all or a subset of T cells, respectively) with complement (C') ablate MLC-generated Tc activity against allogeneic normal cells but do not decrease lysis of HLA-negative, NK-sensitive K562 leukaemia cells by NK, poly I:C-activated NK or MLC-activated NK-like cells. In contrast, OKM1 monoclonal antibody (reactive with a low proportion of non-adherent mononuclear cells as well as macrophages) with C' causes marked diminution of NK and poly I:C-activated NK-cell activity.