The effect of treatment with recombinant human erythropoietin on skeletal muscle was investigated in 11 anemic transfusion-dependent patients on the hospital hemodialysis program. There were no significant changes in anthropomorphic measurements during the study, but the maximum voluntary contraction increased significantly for each muscle group studied (pre-erythropoietin and post-erythropoietin values, respectively, were as follows: biceps, median 170 N [range, 83 to 220 N] v 189 N [range, 89 to 245 N]; triceps, 88 N [range, 59 to 167 N] v 106 N [range, 95 to 185 N]; deltoid, 168 N [range, 78 to 247 N] v 193 N [range, 93 to 290 N]; and quadriceps, 202 N [range, 165 to 300 N] v 265 N [range, 185 to 335 N]; P < 0.05). There were no significant changes in muscle strength in a control group of regular hemodialysis patients. Programmed electrical stimulation of the quadriceps following erythropoietin treatment resulted in both a greater force generated and a longer duration of contraction. Following cessation of the electrical stimulus the relaxation rate for the type II fibers was quicker following erythropoietin therapy. This suggests that some of the benefit observed in physical well-being following correction of the anemia of chronic renal failure with erythropoietin is due to an improvement in voluntary skeletal muscle function.