The cardiovascular effects of anesthetic doses of IV fentanyl (up to 50 μg/kg) and these doses of fentanyl plus diazepam (10 mg) were determined in 23 patients breathing O2 prior to mitral valvular replacement. Fentanyl was administered IV at 50 to 200 μg/min until the patients were unresponsive to verbal command and pinprick stimulation of the chest. Succinylcholine was then administered, the trachea in-tubated, respirations controlled to maintain Paco2 between 30 and 35 torr, and additional fentanyl given until each patient had received 50 μg/kg of fentanyl. Following this, 10 patients received diazepam (10 mg IV) over a 20-second period. Cardiovascular data were recorded before and after every 10 pg/kg of fentanyl (up to 50 μg/kg) and 2, 4, 6, and 8 minutes after diazepam. During the ensuing operation additional fentanyl was administered whenever blood pressure or heart rate increased 15% or more above preanesthetic values. Unresponsiveness was achieved with an average of 11 ± 3 μg/kg of fentanyl. Patients receiving fentanyl alone required total doses of 74 ± 10 μg/kg fentanyl for the entke operation, while those given fentanyl plus diazepam needed 69 ± 9 μg-/kg fentanyl. Fentanyl (20 μg/kg) decreased heart rate and arterial blood pressure but did not significantly change stroke volume, cardiac output, central venous pressure, or peripheral arterial resistance. Additional fentanyl did not further alter heart rate or arterial pressure nor change any other variable measured. Addition of diazepam after fentanyl decreased stroke volume, cardiac output, blood pressure, and peripheral resistance and increased central venous pressure but did not alter heart rate. These data demonstrate that anesthetic doses of fentanyl and O2 produce minimal changes in cardiovascular dynamics but that addition of diazepam after large doses of fentanyl results in cardiovascular depression. Our findings suggest that fentanyl-O2 anesthesia may be an attractive alternative to morphine anesthesia in patients with little cardiac reserve.