Patients on hemodialysis are prone to infection. Neutrophils are the host's first line of defense against certain invading pathogenic microorganisms. Since apoptotic neutrophils are functionally compromised we examined the effect of dialysis membranes on neutrophil apoptosis. Dialysis patients showed greater (p < 0.001) neutrophil apoptosis when compared with control subjects. Cellulose acetate membranes directly promoted (p < 0.001) neutrophil apoptosis. Cellulose acetate membrane-treated neutrophils exhibited greater apoptosis (p < 0.01) when compared with polysulfone membrane-treated neutrophils. Superoxide dismutase (SOD) partly inhibited the cellulose acetate membrane-induced neutrophil apoptosis, whereas both catalase and dimethylthiourea (DMTU) inhibited the polysulfone membrane-induced neutrophil apoptosis. Similarly, L-NAME, a nitric oxide synthase inhibitor, attenuated both the cellulose acetate and the polysulfone membrane-induced neutrophil apoptosis. In addition, cellulose acetate and monocyte interaction products promoted (p < 0.001) neutrophil apoptosis. These results suggest that dialysis membranes can promote neutrophil apoptosis directly as well as through their interaction with monocytes. The direct effect of dialysis membranes seems to be mediated partly through the generation of reactive oxygen species.