Serum erythropoietin (SEP) concentration was measured on two occasions in 42 patients with terminal renal failure (1) immediately before the first hemodialysis, and (2) 3 to 27 months following the onset of regular hemodialysis treatment. Although the hematocrit (Hct) showed an increase in every patient, the SEP concentration decreased in every patient. The mean Hct rose frm 21.7 to 28.6% (volume per volume) P < 0.001), and the SEP dropped from 509 to 182 mU/ml (P < 0.001). This shows that anemia improvement is not a consequence of increased erythropoietin production but that it is most likely due to elimination of an inhibitor of the bone marrow by hemodialysis treatment. The decrease of SEP concentration has to be interpreted as a response to the improved tissue oxygenation that correlates with the hjigher hematocrit or as a consequence of further reduction of renal mass with progress of the renal disease.