We investigated the inhibitory effect of autologous sera on erythroid colony formation (CFU-E) of bone marrow cells from patients with chronic renal disease and the clinical effect of recombinant erythropoietin. Colonies formed in cultures using autologous serum (AS) decreased in 15 among 30 cases as compared with those using fetal calf serum (FCS). This inhibitory effect of autologous sera was diminished by treatment with activated charcoal in all these cases. The degree of hemoglobin increase after administration of recombinant erythropoietin appeared to correlate with the intensity of inhibitory activity of AS. These data indicate the clinical significance of the inhibitor(s) of erythropoiesis in uremic sera and suggest that the clinical effects of erythropoietin in this disease are further improved if the inhibitor(s) can be effectively removed.