The coronary response to acetylcholine was evaluated in 10 patients who had had cardiac transplantation 1 to 8 years earlier and in 4 patients who did not undergo transplantation. All 14 patients had no angiographic evidence of fixed coronary arterial narrowing. Acetylcholine was infused in 10-fold increasing concentrations (10(-6) to 10(-2) M) into the midpoint of the left anterior descending coronary artery by an infusion catheter. Administration was terminated when either vasoconstriction was noted at fluoroscopy or when the maximal acetylcholine concentration was reached. Vascular responses were evaluated by quantitative angiography. All 14 patients had a decrease in coronary lumen size in response to acetylcholine. The mean percentage of vasoconstriction was 37 +/- 24% (p less than 0.001). Combined infusion of nifedipine and the maximal vasoconstricting dose of acetylcholine did not result in a significant reversal of coronary vasoconstriction in all 10 cardiac transplantation patients. It was concluded that acetylcholine is a potent coronary vasoconstrictor in patients who had cardiac transplantation and possibly lacks vasodilating effects in most normal patients without angiographic evidence of coronary artery disease, thus suggesting that acetylcholine might not be a suitable pharmacologic agent for testing endothelial cell integrity.