Plasma concentrations of fentanyl achieved during high dose fentanyl (25 to 75 μg/kg)-oxygen anesthesia were measured during and after fentanyl infusion and during and after cardiopulmonary bypass in patients with coronary artery disease. In addition, the cardiovascular effects of addition of nitrous oxide during fentanyl-oxygen were evaluated at two different plasma concentrations of fentanyl. Intravenous fentanyl (18 ± 4 μg/kg) produced unconsciousness and resulted in a mean plasma fentanyl concentration of 34 ± 7 ng/ml. Plasma fentanyl increased to 48 ± 8 ng/ml after 25 μg/kg, remained relatively constant for the remainder of the fentanyl infusion, and decreased slowly after termination of infusion. Plasma fentanyl was further decreased (to approximately 40% of peak values) with initiation of cardiopulmonary bypass but underwent little further change throughout the remainder of bypass or for 1 hour after bypass. Fentanyl (25 μg/kg) produced small decreases in mean arterial, pulmonary artery, and pulmonary capillary wedge pressures, and systemic and pulmonary vascular resistances. Additional fentanyl produced no further change in these variables. Fentanyl did not significantly change heart rate, cardiac output, or right atrial pressure at any time during the study. Addition of nitrous oxide to the inspired mixture of gases produced significant but similar decreases in cardiac output and increases in heart rate and pulmonary and systemic vascular resistances both before operation and after bypass. These data indicate that anesthetic doses of fentanyl result in plasma fentanyl concentrations that decay more slowly than analgesic doses of the compound. In addition, they demonstrate that while high dose fentanyl-oxygen anesthesia does not appreciably alter cardiovascular dynamics, addition of nitrous oxide results in significant cardiovascular depression which is similar with both high (before operation) and low (after bypass) plasma concentrations of fentanyl.