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 × 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 < 0.001) and their hemoglobin concentration from 86 ± 8 to 117 + 11 g/l (p < 0.001). Their exercise capacity, measured by a standardized exercise test on a bicycle ergometer, increased from 128 ± 45 to 147 ± 57 W (p < 0.01). The control group did not change their THb (349 ± 124 and 357 ± 131 g), hemoglobin (93 ± 8 and 94 ± 10 g/l) 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 < 0.005). The GFR was unchanged in both groups (EPO group: 10 ± 4 and 10 + 6 ml/min × 1.73 m2; control group: 8 ± 3 and 8 ± 3 ml/min × 1.73 m2). The median renal plasma flow did not change significantly in either group (EPO group: 42 and 27 ml/ min × 1.73 m2; control group: 34 and 28 ml/min × 1.73 m2). The median filtration fraction, however, increased significantly in the EPO group (0.21 to 0.30; p < 0.05), while the filtration fraction in the control group was unchanged (0.22 and 0.25; NS). We conclude that erythropoietin treatment increases the THb in predialytic uremic patients, resulting in an improved exercise capacity w