Patients on maintenance hemodialysis with a family history of essential hypertension are at higher risk for increased arterial blood pressure when treated with erythropoietin than patients without family history. This study was performed to elucidate the role of endogenous erythropoietin in essential hypertension. We conducted a study in 42 untreated patients (mean age, 51 +/- 9 years) with essential hypertension World Health Organization stages I or II. Ambulatory 24-hour blood pressure (Spacelab 90207), cardiac output (2D guided M-mode echocardiography and CW Doppler sonography), renal hemodynamics (para-aminohippurate and inulin clearance), and endogenous erythropoietin (radioimmunoassay) together with erythrocyte count, hemoglobin, and hematocrit were measured in parallel. Mean 24-hour systolic blood pressure was 145 +/- 13 mm Hg, and mean diastolic blood pressure was 93 +/- 8 mm Hg. The average erythropoietin concentration was 15.3 +/- 3.7 mU/mL and within the normal range. We found that the higher erythropoietin concentrations, the more elevated was both 24-hour ambulatory systolic (r = 0.51, P < 0.005) and diastolic blood pressure (r = 0.49, P < 0.005). Also, the concentration of endogenous erythropoietin was correlated with total peripheral resistance as noninvasively determined by echocardiographic and Doppler sonographic measurements (r = 0.40, P < 0.02 and r = 0.49, P < 0.02, respectively). With increasing erythropoietin concentrations, renal plasma flow and renal blood flow were found to be progressively reduced (r = -0.32, P < 0.05 and r = -0.35, P < 0.05, respectively) and renal vascular resistance increased (r = 0.41, P < 0.01). Neither hematocrit nor hemoglobin nor erythrocyte count were related to endogenous erythropoietin concentrations. In human essential hypertension, the level of arterial blood pressure is related to endogenous erythropoietin, which is hemodynamically mediated by an increase of total peripheral resistance. Because erythropoietin has shown proliferative and vasoconstricting effects on the endothelium in experimental studies, we suggest that endogenous erythropoietin might be an aggravating or even a promoting factor in the pathogenesis of essential hypertension.