BACKGROUND/AIMS: It has been shown that circulating tumor necrosis factor alpha (TNF-alpha) is elevated in end stage renal disease patients: however, the relationship between TNF-alpha and the development of infection in these patients is unknown. In this study, we investigated the association of plasma TNF-alpha and interleukin 6 (IL-6) with infection in peritoneal dialysis (PD) patients. We also evaluated the association of their plasma levels with the production by peripheral blood mononuclear cells (PBMC), and with various clinical parameters. METHODS: We enrolled 32 patients on maintenance PD and 10 healthy controls. Plasma and PBMC were isolated from blood. PBMC were stimulated with lipopolysaccharide in vitro. RESULTS: Mean follow-up duration was 775 days. Six patients developed organ infections (five pneumonia and one liver abscess), and six patients developed PD peritonitis and eight developed exit site infection. Plasma TNF-alpha and IL-6 levels were significantly elevated in organ infections but not in peritonitis or in exit site infection. Plasma TNF-alpha was the only significant risk factor for organ infections and pneumonia in multivariate regression analysis. Patients with high plasma TNF-alpha levels showed a significantly greater cumulative hazard rate for organ infections compared to those with low TNF-alpha levels. Plasma TNF-alpha levels correlated with TNF-alpha production by PBMC and showed an inverse association with Kt/V. CONCLUSIONS: This is the first study showing that plasma TNF-alpha is a significant risk factor for infection in PD patients.