Treatment with recombinant human erythropoietin (rHuEPO) has solved the problem of anemia in patients on dialysis. However, its application to predialysis patients has raised some doubts about its effects on the progression of renal disease and on blood pressure (BP) and hemodynamic regulation. We have prospectively studied over at least 6 months a group of 11 predialysis patients receiving rHuEPO treatment (initial dose, 1,000 U subcutaneously three times a week). Clinical assessment and biochemical and hematologic measurements were made once every 2 weeks. Twenty-four-hour ambulatory BP monitoring, echocardiography, and determination of neurohumoral mediators of hemodynamics were performed once every 3 months. An adequate hematologic response was found (hemoglobin, 11.7 +/- 0.4 g/dL v 9 +/- 0.3 g/dL) without changes in the progression of renal disease. A decrease in cardiac output and an increase in total peripheral resistance was seen as anemia improved. A trend toward decreased left ventricular (LV) thickness and a significant decrease in LV mass index (from 178.2 +/- 20.6 g/m2 to 147.3 +/- 20.6 g/m2) were observed. Blood pressure control did not improve; moreover, in some patients an increase in systolic values was detected by ambulatory BP. Casual BP remained seemingly stable. Sequential determinations of neurohumoral mediators of hemodynamic substances (endothelin, renin, norepinephrine, epinephrine, dopamine) failed to explain these results. Ambulatory BP reveals a worse control in some patients who were previously hypertensive and confirms the utility of this technique in the assessment of patients under erythropoietin treatment. The trend toward LV hypertrophy regression without improved BP control confirms the role of anemia among the multiple factors leading to LV hypertrophy in end-stage renal disease (ESRD), and opens therapeutic possibilities. Better control of BP may avoid a potential offsetting of beneficial effects that correcting anemia would have on the cardiovascular system.