The safety and efficacy of esmolol during high-dose fentanyl anesthesia were studied in 37 patients undergoing coronary artery bypass grafting (CABG). The anesthetic management consisted of fentanyl 75 μg/kg, pancuronium 0.15 mg/kg, and O2. To assess the safety of esmolol, it was administered in a double-blind manner to 17 anesthetized patients prior to surgical incision. Infusion of the drug was increased in stepwise fashion to obtain administration rates between 100 and 300 μg · kg−1' min−1. Esmolol produced smail but significant increases in pulmonary capillary wedge pressure (PCWP) (8.3 ± 1.7 to 13.2 ± 2.0 mmHg) when compared with placebo (10.9 ± 1.0 to 12.1 ± 0.6 mmHg) (P < 0.05). For the other studied parameters (heart rate, mean arterial pressure, central venous pressure, cardiac index, stroke index, left ventricular stroke work index, systemic vascular resistance, and peripheral vascular resistance), no significant differences were observed between esmolol and placebo. To evaluate the efficacy of esmolol, 20 patients were randomly assigned to an esmolol group (n = 11) or a placebo group (n = 9). The study medication was infused from 5 min before induction through initiation of cardiopulmonary bypass. Infusion of esmolol at 200 μg · kg−1· min−1prevented tachycardia in response to intubation. In the esmolol group the heart rate increased from 63.4 ± 2.7 to 67.6 ± 2.9 beats/min after intubation, while in the placebo group it increased from 61.4 ± 4.3 to 72.4 ± 3.4 beats/min (P < 0.05). Furthermore, the increases in mean pulmonary artery pressure and PCWP observed in unstimulated, anesthetized patients were absent during surgical stimulation. Thus, in CABG patients anesthetized with fentanyl, esmolol appears safe and effective in preventing increases in heart rate during stimulation.