Hypotension during septic shock, which may reflect increased synthesis of the potent vasodilator nitric oxide (NO), is often refractory to vasoconstrictors. We describe the effects of NO synthase inhibition in two patients with life-threatening septic shock in whom conventional therapy had failed to restore blood pressure. NG-monomethyl-L-arginine (L-NMMA) caused dose-dependent increases in blood pressure and systemic vascular resistance in both patients, and a similar effect was observed in the second patient after treatment with NG-nitro-L-arginine methyl ester (L-NAME). These findings indicate that NO synthase induction contributes to the pathogenesis of septic shock, and that inhibition of NO synthase may represent a novel therapeutic option.