Erythropoietin (rHuEPO)-induced hypertension represents a clinical problem in hemodialysis units. However, the underlying molecular mechanisms of this side effect are still unclear. In order to assess the potential participation of the endothelial-derived vasoactive factors, nitric oxide and endothelin-1, bovine aortic endothelial cells were incubated in the presence of rHuEPO. The latter (0.1-10 U/ml, 1-24 h) did not modify the synthesis of nitric oxide and endothelin-1 or the expression of nitric oxide synthase and pre-pro-endothelin-1 mRNAs. These results suggest that endothelial-derived vasoactive factors are not a key component in the hypertensive response observed in certain patients after the administration of rHuEPO.