In an intact closed-chest dog preparation, 2–3 MAC (0.44 per cent alveolar) methoxyflurane markedly decreased left ventricular function and myocardial blood flow, efficiency, and oxygen uptake A negative myocardial excess lactate and unchanged cardiac output–myocardial blood flow ratio suggested adequate myocardial oxygenation. The significant correlation between myocardial blood flow and mean aortic blood pressure in the depressed heart may indicate a loss of metabolic control of coronary perfusion. Myocardial uptake of nonesterified fatty acids, lactate, and pyruvate decreased with myocardial depression. Although there was little glucose utilization in the depressed hearts, arterial glucose was low in contrast to the arterial level with halothane. Consequently, altered myocardial glucose metabolism cannot be postulated as a mechanism in the cardiac depression produced by methoxyflurane.