We studied whether post-renal transplant erythrocytosis (PRTE) could be corrected by enalapril with minimal side-effects, thus avoiding iterative phlebotomies or bilateral nephrectomy of native kidneys. From our renal transplant patients, 12 presented a true PRTE as defined by a 51-Cr red blood cell mass (RBCM) above 32 ml/kg for women and above 36 ml/kg for men. Secondary polycythemia was ruled out: all the patients had a normal renal artery pulsed ultrasonography; in all cases the blood arterial 02 saturation was above 96%. Bone marrow aspiration and histology were performed for each patient: none of them showed evidence of Vaquez disease. All of them had stable renal function i.e. the mean serum creatinine was 112.8 +/- 26.3 mumol/l. They all received the same immunosuppression: azathioprine; ciclosporine A; methylprednisolone. PRTE occurred within the first year post transplant (median 7.5 months; range: 2-34). Their mean RBCM was 37.38 +/- 2.7 ml/kg. Their mean serum value of Epo was 17.41 +/- 13.5 mU/ml (range: 9.1-54). After informed consent, all patients received enalapril starting with 5 mg/day, progressively increased to 20 mg/day, if necessary, in order to maintain the hematocrit below 45%. The mean daily dosage of enalapril was 13.75 +/- 6.1 mg (range: 5-20). The mean follow-up was 14.8 months (range: 3.5-29.5). There was no change in renal function (mean serum creatinine: 126.3 +/- 35 mumol/l). A successful response to enalapril was obtained with a median of 40 days (range: 20-120). 11 patients out of 12 responded to enalapril with a decrease of Hb (14 +/- 2 g/dl vs 16.8 +/- 1.04 g/dl; p = 0.0006) and Ht (41.9 +/- 6.17% vs 51.14 +/- 2%; p = 0.0002) without a significant decrease of Epo (8.1 +/- 3.87; p = 0.1). One patient did not respond to enalapril nor to captopril, but did respond to a combined treatment of enalapril and theophilline. Moreover, all PRTE patients but two did not have Epo levels, before enalapril, above the normal range, suggesting mechanisms other than Epo overproduction by native kidneys i.e. erythropoiesis dysregulation. In conclusion, all patients but one were successfully treated by enalapril without side effects. The treatment was effective as early as 3 weeks from the start and avoided the need for iterative phlebotomies and nephrectomy of native kidneys.