OBJECTIVE Despite its widespread use, little is known about sevoflurane's physiologic effects. The direct myocardial effects of sevoflurane were compared with both halothane and isoflurane. METHODS Administration of minimum alveolar concentration (MAC) fractions of anesthetic (0 to 3.0) was systematically varied to decrease the possibility of time-related effects on measured parameters. METHODS Isolated rat hearts were perfused using a working heart model where the parameters affecting myocardial work were carefully controlled and monitored. METHODS To avoid confounding effects of prior anesthetic administration, hearts were removed from rats, after decapitation, in the absence of anesthetic. METHODS In the first series, isolated perfused rat hearts were exposed to one of the three anesthetics in doses of 0 to 1.5 times MAC. In the second series, hearts were exposed to either sevoflurane or isoflurane in doses of 0 to 3.0 times MAC. The following variables were measured: the rate of change of left ventricular pressure; aortic flow rate; cardiac output; left ventricular end-diastolic pressure; the time constant of isovolumetric relaxation; and coronary vascular resistance. Oxygen consumption was measured during the first series. RESULTS In the first series, all systolic variables were reduced in the presence of halothane when compared with either isoflurane or sevoflurane. Halothane affected diastolic function to a greater degree than either sevoflurane or isoflurane, as measured by the rate of relaxation and end-diastolic pressure. In the second series, at a dose of 3.0 times MAC, both sevoflurane and isoflurane decreased systolic and diastolic function, with a greater reduction in cardiac output, and peak aortic flow and higher left ventricular end-diastolic pressures observed with isoflurane. Coronary resistance and oxygen consumption were not affected by any of the anesthetics. CONCLUSIONS These data suggest that sevoflurane depresses cardiac function less than either halothane in doses of 1.0 and 1.5 x MAC or isoflurane at doses of 3 x MAC.