To assess whether treatment with a dihydropyridine calcium antagonist can prevent the development of hypertension and renal dysfunction after heart transplantation, 38 patients receiving cyclosporine for immunosuppression were randomized shortly after cardiac transplantation to placebo or amlodipine 2.5 mg/day using a double-blind design. The dose was gradually increased to 10 mg/day as tolerated. At 1, 3, 6, 9, and 12 months, 24-hour ambulatory blood pressure (BP) monitoring was performed for the assessment of BP load, echocardiography for the assessment of left ventricular function and mass, 24-hour urine collection for creatinine clearance, and blood sampling for cyclosporine levels. In the placebo group, BP showed modest increases during follow-up, whereas creatinine clearance decreased by about 10 ml/min. In contrast, in the amlodipine group, systolic BP decreased by 15 to 20 mm Hg and diastolic BP by 7 to 10 mm Hg, whereas creatinine clearance tended to increase. Between-group differences were significant as well. During follow-up, left ventricular mass and function showed small decreases, similar for the 2 groups. Cyclosporine doses and blood levels did not differ during follow-up. In conclusion, the initiation of treatment with the dihydropyridine amlodipine shortly after cardiac transplantation represents an effective strategy to maintain normal BP and renal function for > or =1 year.