Post-transplant erythrocytosis (PTE), defined as a persistently elevated hematocrit above 51% after renal transplantation, affects 10% to 15% of graft recipients and usually develops 8 to 24 months after surgery. Thromboembolic events occur in 10% to 30% of the cases; 1% to 2% eventually die of associated complications. The pathogenesis and mechanisms of both the problem and the therapy strategy are unknown, although phlebotomy has previously been the treatment for PTE. We performed a prospective study evaluating impact of enalapril on 62 of 527 recipients (11.7%) with PTE lasting more than 6 months who developed polycythemia and had no other cause for their erythrocytosis. Sixty patients (7 women, 53 men, average age 37.08 +/- 10.36 years) were included in the present study. Patients were treated with enalapril for six months and were reviewed each month. Enalapril, initiated at a dose of 2.5 mg/day and increased to 7+/- 3.15 mg/day, led to a progressive and significant fall in haemoglobin and hematocrit compared to the basal values at any time interval considered, with a maximum reduction at 6th month for haemoglobin (18.2 +/- 0.96 vs. 15.36 +/- 1.43 g/dl, P < 0.0005) and hematocrit (55.49 +/-2.97vs. 45.9 +/- 4.13%, P < 0.0005). Fifty six patients (93.3%) completely responded to enalapril and 3 cases (5%) had partial responses with a significant decrease in Hb and Ht, the mean time of response being 2.5+/-2.0 months. Renal function and kalemia were followed-up during the treatment. Serum creatinine and potassium remained relatively stable throughout the study. Treatment was well tolerated by all patients who completed the study without major adverse side-effects. No patient required phlebotomy and no thromboembolic event occurred during angiotensin-converting enzyme therapy. In conclusion, our results suggest that enalapril is a safe and effective long-term therapy for post-renal transplant erythrocytosis.