Anemia is already present in patients with moderate renal failure and is a major cause of the decline in exercise capacity seen in these patients. We examined the effects of erythropoietin (EPO) treatment in 12 predialytic uremic patients (EPO group: mean age 46 +/- 12 years; 6 men, 6 women) with a mean glomerular filtration rate (GFR) of 10 +/- 4 ml/min x 1.73 m2. These patients were compared to a control group of 8 patients (5 men, 3 women). The observation period was 3 months. The EPO group received 300 U/kg body weight i.v. once a week. The EPO group increased their total hemoglobin (THb) from 323 +/- 89 to 466 +/- 128 g (p less than 0.001) and their hemoglobin concentration from 86 +/- 8 to 117 +/- 11 milligrams (p less than 0.001). Their exercise capacity, measured by a standardized exercise test on a bicycle ergometer, increased from 128 +/- 45 to 147 +/- 57 W (p less than 0.01). The control group did not change their THb (349 +/- 124 and 357 +/- 131 g), hemoglobin (93 +/- 8 and 94 +/- 10 milligrams) or exercise capacity (98 +/- 49 and 101 +/- 50 W) during the observation period. There was a significant correlation between the increase in THb and the increase in exercise capacity in the EPO group (r = 0.81, p less than 0.005). The GFR was unchanged in both groups (EPO group: 10 +/- 4 and 10 +/- 6 ml/min x 1.73 m2; control group: 8 +/- 3 and 8 +/- 3 ml/min x 1.73 m2).(ABSTRACT TRUNCATED AT 250 WORDS)