Patients with heart failure demonstrate attenuated endothelium-dependent vasodilation of the peripheral circulation, while this is suggested to be reversed after heart transplantation. However, data from human subjects are limited and conflict with studies on the peripheral vasomotor tone in cyclosporine-treated animals, suggesting endothelial dysfunction. We recorded forearm skin perfusion responses following graded iontophoresis of 1% acetylcholine (endothelium-dependent) and 1% sodium nitroprusside (endothelium-independent) by laser Doppler perfusion measurements in 32 heart transplant recipients and 15 age-matched controls. In addition, the hyperemic response to 3 min of blood flow occlusion to the forearm was measured on the third finger pulp. With comparable baseline values, the increases in perfusion to the 4 applications of acetylcholine were significantly attenuated in heart transplant recipients compared with controls: 59 +/- 9 vs. 146 +/- 32, 242 +/- 39 vs. 492 +/- 77, 480 +/- 66 vs. 845 +/- 120 and 699 +/- 77 vs. 993 +/- 139% (mean +/- SEM; all p < 0.01). Peak hyperemia (134 +/- 4 vs. 153 +/- 12 arbitrary units (AU); p < 0.05)), time for the hyperemic perfusion to return to preocclusive baseline (52.4 vs. 102.9 s; p < 0.01) and hence the area under the perfusion curve (1469 +/- 244 vs. 4581 +/- 921 AU s; p < 0.01) were reduced among heart transplant recipients. The area under the perfusion curve correlated significantly with mean arterial blood pressure (r = -0.60; p < 0.01) and with the responses to iontophoresis of acetylcholine (r = 0.41; p < 0.01). Two non-invasive tests of vascular function demonstrate attenuated endothelial-dependent microvascular responses in heart transplant recipients. The relative impact of prior congestive heart failure and postoperative factors, such as treatment with cyclosporine, remains to be determined.