We tested the effect of urinary TNF-binding protein (uTBP) on the toxic effect of TNF (0.5 micrograms/mouse, i.v.) in adrenalectomized mice sensitized with IL-1 to increase susceptibility to TNF. In this experimental model, mortality was 67%, but decreased to 13% when uTBP (250 micrograms/mouse, i.v.) was administered simultaneously with TNF. The protective effect of uTBP was dose-dependent, and time course experiments indicated a protective effect when uTBP was administered before or up to one hour after TNF. Some protection was also obtained when uTBP was given three hours after TNF. Urinary TBP improved the survival of mice after a lethal dose of LPS (1.2 mg/mouse, i.p.), suggesting its possible efficacy in the therapy of septic shock or other TNF-mediated pathologies.