Hypotension in septic shock is often resistant to treatment with vasoconstrictors and appears to be mediated by production of nitric oxide (NO). Reversal of endotoxin-induced hypotension in rats was achieved by intravenous injection of 30 mg/kg NG-monomethyl-L-arginine (L-NMMA), an inhibitor of endogenous NO synthesis. A lower dose of 3 mg/kg L-NMMA was ineffective, but 300 mg/kg L-NMMA accelerated and enhanced the fall in blood pressure. NO synthase inhibitors may be helpful in the treatment of hypotension associated with sepsis or therapeutic use of cytokines, but complete inhibition of endogenous NO synthesis may be counterproductive.