In 14 severely anemic patients with end-stage renal disease and chronic hemodialysis the effect of recombinant human erythropoietin (EPO) on hemopoiesis was investigated. Bone marrow biopsies were taken before and after four and 26 months of treatment with EPO to evaluate quantitative and qualitative changes of histomorphology. EPO induced normalization of maturation and an increase in cell mass of the erythropoietic line in all patients. The number of megakaryocyte also increased significantly with EPO treatment (P less than 0.01). At the time of the third bone marrow biopsy (26 months) erythropoiesis was normal. Megakaryopoiesis remained unchanged compared to the second biopsy (4 months). No cytomorphologic abnormalities or other evidence for malignant disorder could be detected in any of the patients. Hematocrit increased from a mean of 19 to 31 percent at the second evaluation (P less than 0.001). Platelet count had risen by a mean of 30,000 at four months (P less than 0.05) and slightly decreased at 26 months. These observations suggest great safety of long-term treatment with recombinant human erythropoietin, and demonstrate efficacy in correcting reduced and immature erythropoiesis in chronically hemodialyzed patients. EPO also stimulates human megakaryopoiesis.