Recombinant human erythropoietin (r-HuEPO) is an established tool for correction of renal anemia. It is well known that chronic administration of r-HuEPO often causes hypertension in dialysis patients. However, the mechanism of the r-HuEPO induced hypertension has not been fully elucidated. We report a case of r-HuEPO induced hypertension in an anephric patient. In this case, hemodialysis was started after removal of both kidneys because of rupture of an angiomyolipoma. Although mean blood pressure (BP) did not change during the period of rapid correction of renal anemia by blood transfusion, treatment with r-HuEPO significantly increased mean BP. Also, discontinuation of r-HuEPO resulted in a decrease in mean BP. These results suggested that r-HuEPO caused an elevation in BP in the absence of kidneys, and the elevation in BP was thought to be independent of an increase in hematocrit level or hypervolemia. We also investigated the role of nitric oxide (NO) in r-HuEPO induced alteration of BP. A significant negative correlation was found between a decrease in serum NO level and an increase in mean BP during the period of r-HuEPO administration. The results suggest that an inhibitory effect of r-HuEPO on NO production might be, at least in part, related to the r-HuEPO induced hypertension in this case.