Experiments were designed to determine the effects of fentanyl on coronary vascular tone and energetic state of the heart. Both arterial and arteriolar responses were assessed; particular attention was directed to epicardial vessels. Four experimental methods and three animal species were used. Isolated canine coronary artery rings with and without endothelium were suspended in organ chambers, and changes in their tension were measured. Fentanyl (100 ng/ml) had no effect on resting tension of unstimulated rings on a contraction evoked by serotonin 10(-8) to 10(-4) M. In rings with endothelium, the opioid had a minimal depressant effect on the contractile response to phenylephrine. Tension of vessels precontracted with serotonin (3 x 10(-7) M), or phenylephrine (10(-5) M) was unchanged following fentanyl at 10, 30, 70, or 150 ng/ml. Computerized quantitative angiography was used in intact pigs anesthetized with ketamine to determine the effects of fentanyl on coronary artery diameters of vessels with or without endothelium. Intravenous fentanyl 50 and 250 micrograms/kg had no effect on vessel diameters. Isolated perfused rat hearts were used to assess fentanyl effects upon coronary flow and arteriolar tone and upon myocardial energy state. Coronary blood flow was not altered by fentanyl (100 ng/ml) and was unchanged following washout of the drug. The heart maintained a normal energy status prior to and following fentanyl treatment. These data demonstrate that, under the conditions tested, fentanyl is devoid of major effects on the coronary circulation and upon myocardial metabolism.