Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) were determined in the plasma of long-term hemodialysis (HD) patients and uremic (UR) patients undergoing their first dialysis session using either cellulosic (CUP) or synthetic (PAN-AN 69) membrane-equipped dialyzers. In long-term HD patients, plasma IL-1 and TNF alpha levels were significantly increased compared to their levels in normal subjects. During a single dialysis session, a significant increase in IL-1 but not in TNF alpha was observed. In not yet dialyzed UR patients, IL-1 plasma levels did not differ from those observed in normal subjects. By contrast, TNF alpha was found significantly increased although less than in long-term HD patients. During the first dialysis session, no significant increase was observed in the levels of either monokine. Lastly, regardless of the group of patients, no significant influence of the dialysis membrane could be detected, suggesting that the observed changes are not exclusively secondary to the activation of complement. Altogether, these results suggest that the passage of the blood through the extracorporeal dialysis circuit triggers the secretion of IL-1 and further exacerbates that of TNF alpha by monocytes. The presence of increased TNF alpha in the plasma of first-dialysis UR patients suggests that factors unrelated to dialysis contribute to the activation of monocytes in these patients. Lastly, the concomitant presence of IL-1 and TNF alpha in the plasma of long-term HD patients could be responsible for some of the clinical features observed in these patients, and provides strong evidence favoring the concept that HD can be assimilated to a recurrent acute-phase inflammatory response.