In this study we investigated the mechanisms of cytotoxicity mediated by pokeweed mitogen (PWM)-activated human peripheral blood monocytes. By using DNA electrophoresis and propidium iodide (PI)-DNA staining flow cytometry, we demonstrated that apoptotic cell death of target U937 cells and Raji cells was induced in lectin (PWM)-dependent monocyte-mediated cytotoxicity (LDMC). The LDMC-mediated DNA fragmentation in U937 cells and Raji cells was induced in lectin (PWM)-dependent monocyte mediated cytotoxicity(LDMC). The LDMC-mediated DNA fragmentation in U937 cells was completely inhibited by anti-TNF alpha monoclonal antibody (mAb), but not by the addition of monosaccharide (N-acetylglucosamine, GlcNAc, a sugar specifically recognized by PWM and a lectin-like receptor on monocytes). In contrast, GlcNAc inhibited the DNA fragmentation in Raji cells induced by LDMC which the anti-TNF alpha mAb had no effect. PWM was found to stimulate the production of nitric oxide (NO) from monocytes. The NO-production was enhanced in the presence of target Raji cells, while the enhancement was abolished by the treatment with GlcNAc. By flow cytometry, we found that PWM bound to tumour cells as well as monocytes, and inhibited the expression of HLA-DR antigen on tumour cells. These results suggest that the presence of lectin molecules on the surface of monocytes and tumour cells may bring the two cells together, thus facilitating the induction of apoptosis in target cells by triggering the production of cytolytic factors (TNF and NO) and the modification of target cell surface antigen (HLA-DR).