Recombinant erythropoietin (EPO) has been shown to induce vascular smooth muscle contraction in vitro suggesting a rapid acting pressor effect. In addition its chronic administration has been shown to raise plasma endothelin. This study was designed to explore the presence, if any, of fast-acting effects of EPO on the arterial blood pressure and endothelin level in vivo. Nine stable patients with end-stage renal disease (ESRD) were included in a double-blind, crossover, placebo-controlled study using IV bolus injections of either EPO or saline solution administered to patients while they were comfortably seated in reclining chairs and undisturbed in individual climate-controlled rooms. After a 15-min resting period, the bolus injection was given, and blood pressure (BP) and heart rate were measured and recorded automatically every 5 min for 60 min using an electronic device to avoid operator bias/error. In addition, blood samples were obtained for plasma endothelin determination at time 0 and at 5, 30, and 60 min after injection. Patients were studied approximately 2 h before their regularly scheduled dialysis session. The EPO dosage given (50-60 U/kg) was equal to the maintenance dose, routinely administered during dialysis. No significant change was observed in arterial BP, heart rate, or plasma endothelin concentration relative to the baseline values after either EPO or placebo administration. Thus, the results have excluded a rapid effect on BP, heart rate, and endothelin concentration of EPO at therapeutic doses which, when chronically administered, can clearly raise arterial blood pressure in ESRD patients.