Methoxyflurane was administered to eight healthy male volunteers over a three-hour period during which myocardial contractility, cardiac output, oxygen consumption, and total peripheral resistance were measured serially. Myocardial contractile force initially decreased, but returned toward control with time. Cardiac output remained unchanged. Total peripheral resistance, reduced at one hour in most cases, did not decrease further during the next two hours. Oxygen consumption remained directly related to cardiac output. It was concluded that some “adaptation” or “recovery” occurs when methoxyflurane is administered for an extended period, but recovery was not as marked as that observed with halothane.