The protective efficacy of a p55 tumor necrosis factor receptor immunoadhesin (TNFR-IgG) was compared with that of an anti-TNF monoclonal antibody (MAb) in a rat endotoxic shock model. TNFR-IgG (5 mg/kg), given 30 min before endotoxin (LPS), attenuated LPS induction of hypotension and tachycardia and eliminated LPS induction of serum TNF activity. In contrast, anti-TNF MAb (5 mg/kg) had little effect on LPS-induced hemodynamic changes and neutralized only partially the excessive serum TNF activity. The 6-day survival was 1 of 10 controls; 6 of 11, 5 of 7, and 8 of 9 rats receiving 0.2, 1.0, or 5.0 mg/kg TNFR-IgG, respectively; and 3 of 8 rats receiving 5 mg/kg anti-TNF MAb. These results indicate that TNFR-IgG is more potent than anti-TNF MAb at neutralizing excessive TNF activity in vivo.