The objective of this study was to examine peripheral vascular function before and after cardiac transplantation and to assess the effect of immunosuppressive therapy on peripheral vascular reactivity. Peripheral vascular function abnormalities present in congestive heart failure may be reversed with cardiac transplantation, but immunosuppressive therapy may alter these changes in the peripheral vasculature. Venous occlusion plethysmography was used to study peripheral vascular function in nine patients with severe congestive heart failure who underwent cardiac transplantation. Forearm blood flow and forearm vascular resistance were measured in patients with congestive heart failure in response to cold stimulation, maximal hyperemia, and hand grip exercise (1) before transplantation; (2) 24 to 36 hours posttransplantation before the commencement of cyclosporine; (3) 6 to 8 days posttransplantation in the presence of therapeutic cyclosporine levels; and (4) 6 weeks posttransplantation. Venous capacitance was also measured. After cardiac transplantation, mean arterial pressure increased and remained elevated. Forearm blood flow initially increased after transplantation but subsequently decreased with cyclosporine. Cold-induced reflex sympathetic activation decreased immediately after transplantation but was significantly enhanced with cyclosporine. The maximal vasodilatory response following ischemic cuff occlusion and with 5 minutes of isometric hand grip exercise increased significantly after transplantation and remained improved at 6 weeks. Thus after cardiac transplantation, peripheral vasodilator function improves and is not altered by cyclosporine. However, with cyclosporine therapy resting forearm vascular resistance increases and reflex sympathetic vasoconstriction is enhanced, suggesting that cyclosporine may potentiate adrenergic-mediated peripheral vasoconstriction and thus may contribute to posttransplant hypertension.