Tumor necrosis factor-alpha (TNF-alpha) is a cytokine with numerous immunological and metabolic activities. To study the role of TNF-alpha on the pathophysiology of anorexia nervosa and its complications, plasma concentrations of TNF-alpha, 2 soluble TNF receptors (sTNF-RI and sTNF-RII), and leptin were measured in 20 female patients with anorexia nervosa (AN) and 20 age-matched normal women (N). Plasma TNF-alpha concentrations in AN were significantly higher than those in N (4.1 +/- 0.6 pg/mL vs. 1.6 +/- 0.1 pg/mL; P < 0.01). Although no significant difference was observed in plasma sTNF-RI concentrations between the two groups, plasma sTNF-RII concentrations in AN were significantly higher than those in N (2094.0 +/- 138.5 pg/mL vs. 1569.5 +/- 84.0 pg/mL; P < 0.01). Plasma concentrations of TNF-alpha and sTNF-RII after treatment of 8 anorectic patients were not different from those before treatment, although body fat mass and plasma leptin concentrations significantly increased after treatment. Plasma TNF-alpha concentrations were not related to body fat mass in anorectic patients. These results suggest that the adipose tissue may not be the immediate source of TNF-alpha in anorectic patients and that TNF-alpha may contribute to the pathophysiology of immunological and metabolic abnormalities in anorexia nervosa.