Coronary transplant vasculopathy is known to be associated with an early impairment of endothelium-dependent vasodilatation. In this study the largely endothelium-independent dilator response to dipyridamole was evaluated in 22 patients 36 +/- 17 months after transplantation in relation to their angiographic findings. The dipyridamole coronary reserve was measured by N-13 ammonia and positron emission tomography (PET). Transplant vasculopathy was suspected or evident in 13 of 22 patients by coronary angiography. Coronary reserve was lower in transplant recipients than in normal controls (2.3 +/- 0.9 vs. 4.7 +/- 1.4). Those with a normal angiogram had a near normal minimal coronary resistance (0.3 +/- 0.04 mmHg.min.100 g/ml) and a normalized coronary reserve after correction for the increased resting blood flow (4.8 +/- 0.7). However, in patients with angiographic vasculopathy, coronary reserve was markedly reduced (1.8 +/- 0.7, corrected 2.7 +/- 1.0) and minimal coronary resistance was elevated (0.6 +/- 0.3, p < 0.001). Moreover, regional coronary reserve was homogeneously reduced throughout the myocardium without a clear segmental relationship to angiographic stenoses. After testing of other factors known to influence coronary resistance, our data are compatible with diffuse obstructions of the microvascular bed that are associated with an angiographically visible vasculopathy. The evaluation of coronary reserve by dipyridamole and PET provides a useful extension of angiography in these patients.