Background: Desflurane, a fluorinated methyl-ethyl ether, has some advantageous properties including low blood solubility, stability in soda lime, and resistance to biodegradation. Desflurane in vivo has demonstrated myocardial depressant property. The purpose of this study was to test the direct effects of desflurane on myocardial contractile function and coronary flow in the isolated heart. Methods: Twelve isolated rat hearts were continuously perfused with modified Krebs solution containing 6, 9 and 12 vol% of desflurane for 10 min at each concentration. Systolic left ventricular pressure and rate of change of ventricular pressure (dp/dt) were measured. Heart rate and coronary flow were also measured. To differentiate direct vasodilatory effect of desflurane from an indirect metabolic effect due to autoregulation of coronary flow, oxygen delivery, myocardial oxygen consumption and percent oxygen extraction were calculated. Results: Heart rate (control 266+/-22 beats/min) decreased to 250+/-23 beats/min at 6 vol%, 236+/-26 beats/min at 9 vol% and 223+/-22 beats/min at 12 vol% of desflurane. Systolic left ventricular pressure and dp/dt decreased in a concentration-dependent manner. In spite of decrement of myocardial oxygen consumption, coronary flow (control 12.0+/-1.2 ml/min) increased to 12.8+/-1.6 ml/min at 6 vol%, 12.9+/-1.6 ml/min at 9 vol% and 13.7+/-1.4 ml/min at 12 vol% of desflurane. Oxygen delivery increased proportionally with coronary flow. Percent oxygen extraction decreased in a concentration-dependent manner. Conclusion: These results suggest that desflurane has a direct myocardial depressing and coronary vasodilating effect in a concentration-dependent manner.