This study tests the hypothesis that myocardial blood flow and coronary microvascular dilator capacity vary as a function of time after orthotopic heart transplantation in humans. Positron emission tomography measurements of myocardial blood flow were obtained at rest and during adenosine in 24 patients between 1 and 86 months after heart transplantation. At the time of the study all patients were clinically well and had angiographically normal epicardial coronary artery vessels. Patients were divided into 3 groups based on time from transplant to positron emission tomography measurement of myocardial blood flow: group 1 to 12 months (n = 9); group 13 to 34 months (n = 8); and group ≥37 months (n = 7). Basal myocardial blood flow in group 1 to 12 months (1.86 � 1.01 ml/min/g) exceeded (p <0.05) that of group 13 to 34 months (1.17 � 0.73) and group ≥37 months (0.98 � 0.34). In group 13 to 34 months, basal myocardial blood flow and maximal dilator capacity (minimal coronary vascular resistance with adenosine 36 � 12 mm Hg/ml/min/g) were comparable to that of normal volunteers (1.01 � 0.20 and 37 � 9, respectively). In group ≥37 months, maximal flow response to adenosine was reduced (2.54 � 1.25 vs 3.16 � 0.52, respectively, p = 0.06). Maximal dilator capacity in group ≥37 months (60 � 34) was impaired versus group 1 to 12 months (36 � 10) and group 13 to 34 months (36 � 12; both p <0.05) as well as normals (37 � 9, p <0.05). During the first year after cardiac transplantation basal myocardial blood flow is elevated out of proportion to external determinants of myocardial oxygen demand, but maximal dilator capacity of the coronary microcirculation is normal. Between 1 and 3 years both basal myocardial blood flow and microvascular function tend to normalize. After 3 years, although basal myocardial blood flow is normal, microvascular dilator capacity is impaired.