To assess the effect of substantial increases in blood hemoglobin (Hb) caused by treatment with recombinant human erythropoietin (rhEPO) on exercise capacity in maintenance hemodialysis patients, we evaluated 10 patients (7 men and 3 women) at a mean age of 44.3 +/- 8.4 years on maintenance hemodialysis for a mean of 29.7 +/- 30.2 months by treadmill exercise to exhaustion. The patients were tested before administration of rhEPO and after a minimum 1 g/dl rise in Hb. With a change in Hb from 7.1 +/- 1.4 to 9.8 +/- 2.1 g/dl, peak oxygen consumption (VO2 peak) with exercise increased 50.3 +/- 9% (T1 = 15.1 +/- 5.3, T2 = 22.7 +/- 4.6 ml O2/kg/min, p less than 0.05). Respiratory exchange ratio (RER) at a given submaximal exercise level (3 mph, 6% of elevation) decreased significantly (T1 = 1.13 +/- 0.24, T2 = 0.92 +/- 0.08, p less than 0.05). The rhEPO-mediated increase in Hb was associated with an increased VO2 peak--an improvement of the peak exercise capacity and a reduced submaximal RER--reflecting a reduction in anaerobic metabolism at activities of daily living.