The presence of naturally occurring inhibitors of interleukin-1 (IL-1) and tumor necrosis factor (TNF) in a variety of diseases has been demonstrated. The IL-1 receptor antagonist (IL-1Ra) binds to IL-1 receptors and blocks the activity of IL-1, and a soluble form of the p55 TNF receptor (TNFsRp55) binds and neutralizes TNF. In the present study, plasma levels of IL-1 beta, IL-1Ra, TNF alpha and TNFsRp55 were measured in 29 undialyzed patients with chronic renal failure (CRF), 13 patients on continuous ambulatory peritoneal dialysis (CAPD), 42 patients on chronic hemodialysis (HD) and in 15 healthy controls. Of the 29 patients with CRF, 13 had end-stage renal disease (ESRD, estimated GFR < 10 ml/min). Among health controls, plasma levels of IL-1 beta, IL-1Ra and TNF alpha were at or below the limit of detection of the assay. In undialyzed patients with ESRD, or in patients on CAPD or HD, plasma levels of IL-1 beta were 428 +/- 134 pg/ml, 378 +/- 83 and 352 +/- 43 pg/ml, respectively. Although plasma levels of IL-1 beta in each group of patients were higher than those in healthy controls (< 160 pg/ml), these differences were not statistically significant. In contrast, plasma levels of IL-1Ra in undialyzed patients with ESRD (629 +/- 125 pg/ml, P = 0.03), CAPD (902 +/- 164 pg/ml, P < 0.0001) and HD patients (642 +/- 73 pg/ml, P = 0.004) were significantly higher than those in healthy controls (103 +/- 15).(ABSTRACT TRUNCATED AT 250 WORDS)