The anesthetic potency of racemic isoflurane and the optically pure stereoisomers was examined in rats. The (+) isomer was 53% more potent than the (-) isomer (minimum alveolar concentration (MAC) = 1.06 +/- 0.07% vs. 1.62 +/- 0.02%, P < 0.05). MAC for racemic isoflurane was 1.32 +/- 0.03%. Both stereoisomers and the racemic isoflurane produced similar depression of arterial pressure. However, the (+) isomer blunted the cardiovascular response to a painful stimulus to a greater extent than did an equi-MAC dose of the (-) isomer. These are the first data to describe pharmacological differences between stereoisomers of a volatile anesthetic administered in vivo by the conventional route (inhaled) and measuring the clinically relevant index of anesthesia, MAC. These data are consistent with a receptor-mediated anesthetic mechanism by volatile anesthetics.