The effect of erythroid differentiation factor (EDF) on the colony formation of erythroid cells (CFU-E and BFU-E) inhibited by the sera from the patients with chronic renal failure (CRF) was evaluated by methylcellulose assay. EDF restored the inhibited formation of CFU-E colony irrespective of the absence or presence of the accessory cells. In addition, EDF was considered to recover BFU-E colony formation through the burst promoting activity (BPA) secreted by the adherent cells. A suicide experiment using 3H-thymidine revealed that EDF acted to induce BFU-E from resting phase to S phase of the cell cycle. Moreover, the number of circulating BFU-E and the secretion of BPA by the mononuclear cells, both of which were significantly low in CRF patients, were also moderately increased by the addition of EDF. These data suggest that EDF could be utilized as a therapeutic agent for pathogenetic factors except hypoproduction of erythropoietin on the anemia of the patients with CRF.