The production of tumor necrosis factor alpha (TNFα) activity by peripheral blood mononuclear cells (PBMC) was determined in uremic patients on chronic hemodialysis (HD; n = 27), continuous ambulatory peritoneal dialysis (CAPD; n = 19), and in patients with chronic renal failure who were not yet on dialysis (CRF-ND; n = 18). In the HD group blood was taken immediately prior to and immediately following an HD session utilizing a cellulose acetate dialyzer. Post-HD PBMC spontaneously (i.e. in serum free media) produced significantly more TNFα activity than the PB MC of all other patient groups as well as those of the normal controls (n = 41) (p < 0.003). Post-HD PBMC produced significantly more TNFα activity than pre-HD PBMC both spontaneously and in the presence of nonuremic sera (p < 0.003). PBMC prior to HD also produced significantly more TNFα activity than CAPD PBMC and normal PBMC in the presence of autologous heat inactivated sera (p < 0.03). Under some culture conditions (i.e. in the presence of nonuremic sera) normal PBMC produced significantly (p < 0.003) more TNFα activity than CAPD PBMC. Finally, a positive correlation was found between PBMC TNFα activity and age for HD patients (r = 0.7, p < 0.004) but not for CAPD or CRF-ND patients. These findings suggest that PBMC of HD but not CAPD or CRF-ND patients are chronically stimulated to produce TNFα activity. Differences in TNFα activity production by PBMC of HD and CAPD patients may determine, at least in part, the types of short- and long-term complications seen in these patient popu