Leptin is a pleiotropic hormone believed to regulate body weight. Its function in wasting during inflammatory disease in humans is unknown. We studied the effect of repeated tumor necrosis factor (TNF) infusion on serum leptin levels in six patients with solid tumors. TNF infusion on day 1 resulted in an increase in serum leptin levels from 3.1 (SEM +/- 0.28) ng/mL to 5.2 (SEM +/- 0.6) ng/mL after 12 h (P < 0.001). The serum levels returned to baseline within 24 h. Similar results were obtained when TNF was infused on subsequent days. The study shows that leptin serum levels are under control of TNF.