Review of a large renal transplant experience revealed a 17.3% incidence of posttransplant erythrocytosis. The influence of kidney source, pretransplant hematocrit, duration of pretransplant dialysis, renal transplant function, acute rejection, transplant renal artery stenosis, urinary tract obstruction, smoking, diabetes, retention of native kidneys, splenectomy, parathyroidectomy, immunosuppression, hypertension, and liver enzyme abnormalities on the development of erythrocytosis in 53 recipients was determined. Comparison was made with 49 control recipients matched for kidney function, time after grafting, age, and sex. Erythrocytosis occurred 3 to 90 months after transplantation and persisted for 1 to over 84 months. Risk factors for the development of erythrocytosis were smoking, diabetes, and a rejection free course. In contradistinction to previous smaller series, erythrocytosis occurred in patients with good renal function (serum creatinine 1.62 +/- 0.43 mg/dl) without prominence of graft rejection, transplant artery stenosis or obstruction. Despite therapeutic phlebotomy, 11 thromboembolic events occurred in 10 of the 53 patients with erythrocytosis, but in none of the controls (P less than 0.001). The high incidence of erythrocytosis following renal transplantation and the risk of associated thromboembolic events should encourage awareness and controlled evaluation of therapeutic modalities.