Isoflurane is a potent systemic vasodilator. Because isoflurane vasodilation is clinically significant, we sought to explore whether decreases in systemic vascular resistance caused by isoflurane involve the alpha-adrenergic nervous system in humans. Specifically, we tested the hypothesis that isoflurane systemic vasodilation is mediated via inhibition of vascular alpha 1-adrenergic responsiveness. Phenylephrine pressor dose-response curves were established before anesthesia and during isoflurane/oxygen anesthesia in patients undergoing coronary artery bypass surgery; all patients included in the study (n = 11) demonstrated significant (P = 0.0001) decreases in systemic vascular resistance when isoflurane was given in concentrations adequate to produce a 20% decrease in mean arterial blood pressure. Polynomial regression of the phenylephrine dose-response curve was used to estimate the phenylephrine dose required to increase mean arterial blood pressure 15 mm Hg, designated PD15 mm Hg. Each patient served as his or her own control. Preanesthetic baseline PD15 mm Hg values (115 +/- 23 micrograms [1.4 +/- 0.3 micrograms/kg], mean +/- SEM) were not significantly different from isoflurane PD15 mm Hg values (124 +/- 20 micrograms [1.5 +/- 0.3 micrograms/kg]). End-tidal isoflurane concentration ranged from 0.6%-1.5%; isoflurane PD15 mm Hg was not correlated with end-tidal isoflurane concentration. Patient characteristics and hemodynamics did not affect PD15 mm Hg. These results suggest that isoflurane-induced systemic vasodilation is not mediated via inhibition of alpha 1-adrenergic responsiveness, disproving our hypothesis. This finding has clinical importance because it demonstrates that alpha 1-adrenergic stimulation with phenylephrine is effective in correcting hypotension in patients receiving isoflurane anesthesia.