Results of in vivo and in vitro studies of the anesthetic potencies of the enantiomers (optical isomers) of isoflurane provide various results ranging from no difference to differences of nearly two fold. A finding of a difference in anesthetic requirement in the whole animal has particular relevance to theories of anesthetic mechanisms of action because it suggests that anesthesia may result from a specific anesthetic-receptor interaction. This led to our decision to redetermine the minimum alveolar anesthetic concentration (MAC) of (+)-S and (-)-R enantiomers of isoflurane in 12 Sprague-Dawley rats (six per group). The (+)-S enantiomer gave a MAC of 0.0144 +/- 0.0012 atm (i.e., 1.44% +/- 0.12% at 1 atm pressure; mean +/- SD) and the (-)-R enantiomer gave a MAC of 0.0169 +/- 0.0020 atm. Although the 17% greater value for the (-)-R enantiomer is qualitatively consistent with previous results the difference is not significant (P = 0.06), and the absolute difference is smaller than that found by a previous study. However, given the small sample size, our power to define a small significant difference is limited. Regardless of statistical significance, our results do not confirm the conclusion that interaction with a specific receptor is important to the mechanism of action of inhaled anesthetics.