Lentinan, an antitumor polysaccharide, has been assessed for its potential in vivo to augment erythroid progenitor cells and protect them from the cytotoxic effects of antitumor chemotherapeutics. Lentinan augmented the level of burst-forming units-erythroid (BFU-E) and accelerated the recovery of the reduced number of BFU-E in mice treated with 5-fluorouracil (5-FU); lentinan did not influence red blood cell counts or colony-forming unit-erythroid (CFU-E) numbers in the femoral marrow. A significant decrease in stem cell inhibitory factor (SCIF) activities in bone marrow and an increase in colony-forming unit-spleen (CFU-S) formation were observed in the lentinan-treated mice. The mechanism of augmented BFU-E formation may be partly due to augmented production of stem cells, giving rise to both CFU-GM and BFU-E. Furthermore, when lentinan administration was followed by administration of erythropoietin (Epo) in 5-FU-treated mice, increases in femoral marrow and splenic CFU-E formation and augmentation of reticulocyte counts were observed beyond the level observed in mice treated with Epo alone. These results suggest that lentinan may augment the effects of Epo on erythropoiesis in the course of anemia and the decreased erythropoiesis in cancer patients receiving chemotherapy.