During acute rejection, coronary vascular reserve is severely impaired in human orthotopic heart transplants. To evaluate the effects of rejection therapy on coronary vascular reserve, the ratio of peak-to-resting coronary flow velocity was assessed with a coronary Doppler catheter and a maximally vasodilating dose of intracoronary papaverine (12 mg) in nine allograft recipients without rejection (group 1) and in six recipients before and after treatment of an acute episode of rejection (group 2). All the patients had normal epicardial coronary arteries and were free of left ventricular hypertrophy. In group 2 during rejection, the coronary vascular reserve was significantly lower than in group 1, in which all the patients had a peak-to-resting coronary flow velocity ratio greater than 4 (2.3 +/- 0.5 vs. 5.4 +/- 0.8, respectively, p less than 0.001). In group 2 after treatment of rejection, the peak-to-resting coronary flow velocity ratio was similar to that of group 1 (4.7 +/- 0.8). Heart rate, left ventricular volumes and pressures, hemoglobin concentration, and arterial oxygen pressure were similar in the two groups. This study provides evidence that alterations of coronary vascular reserve because of acute rejection were reversible after treatment of the rejection episode.