Accelerated graft atherosclerosis is responsible for increased mortality and morbidity among heart transplant recipients. The aim of this in-vivo study was to evaluate coronary atherosclerotic vessel alterations and endothelial function. Seventeen patients (14 males; mean age 49.3 years; range 24 to 69) were studied an average of 11 weeks (range 5 to 21) after heart transplantation because of coronary artery disease (n = 8), dilative cardiomyopathy (n = 7), mitral valve replacement (n = 1) and left atrial metastases of a leiomyosarcoma (n = 1). Mean age of the donor hearts (9 males) was 29 years (range 12 to 55). All recipients underwent biplane ventriculography and coronary angiography. In this study population, a total of 120 coronary segments (main stem, 21; left anterior descending artery, 85; circumflex artery, 14) were analyzed by intravascular ultrasound (20 MHz, 3.5F). In 13 patients, acetylcholine was infused into the proximal left anterior descending artery (10(-8) to 10(-5) M) to evaluate vasomotion within this segment. Regional contraction abnormalities were documented in 2 patients. Nine segments angiographically showed non-critical stenoses (5 patients). Intravascular ultrasound detected 52 cross-sectional areas with a three-layer pattern indicating intimal thickening. Mean circumferential extension of intimal proliferation was 192 degrees, mean intimal thickness 0.35 mm. Only 5 segments of the sonographically pathological cross-sectional areas showed angiographical evidence of atherosclerotic lesions. Intracoronary administration of acetylcholine at doses of 10(-8) and 10(-7) M resulted in vasoconstriction of the examined coronary segment in only 2 patients; the intracoronary application of acetylcholine at doses of 10(-6) and 10(-5) M revealed coronary vasoconstriction in 10 of the total of 13 patients. Using intravascular ultrasound, coronary artery lesions in heart transplant recipients can already be depicted at a very early stage. The abnormal response to acetylcholine in most of the heart recipients is independent of the extent of atherosclerotic vessel abnormalities documented by ultrasound or angiography.