This study evaluated changes in coronary blood flow (CBF), myocardial oxygen consumption (MVo2), and myocardial segmental shortening (SS) during intracoronary administrations of enflurane in in situ canine hearts. The left anterior descending coronary artery (LAD) of 11 anesthetized and mechanically ventilated dogs was perfused at constant perfusion pressure (80 mm Hg) with enflurane-free blood or with blood equilibrated in an extracorporeal oxygenator with enflurane (1.1%, 2.2%, 4.4%). CBF (measured with a Doppler flow transducer) was multiplied by the local arteriovenous (A-V) O2 difference to calculate MVo2. SS was measured with ultrasonic crystals. Myocardial lactate uptake was assessed. Peak CBF responses during enflurane were compared with those during maximum coronary vasodilation with adenosine. Enflurane caused concentration-dependent increases in CBF, and decreases in MVo2 and SS. The greatest increase in CBF during enflurane (4.4%) was similar to that achievable with adenosine. Myocardial lactate uptake was not affected by enflurane. In conclusion, enflurane has a direct coronary vasodilating effect. The potency of this effect is underscored by the ability of enflurane to cause marked increases in CBF, while appreciably reducing myocardial O2 demand. Since the enflurane-induced reduction in myocardial contractility was not due to ischemia, it likely reflected a direct negative inotropic effect. When the direct effects of enflurane are compared with those of equianesthetic concentrations of halothane and isoflurane previously shown in the same model, enflurane has a coronary vasodilating effect similar to that of halothane but less than that of isoflurane, and it has a negative inotropic effect greater than that of both isoflurane and halothane.