Most anemic patients with chronic renal failure have gastric mucosal lesions. However, these gastric lesions are often improved after the administration of recombinant human erythropoietin (rHuEPO). We have used the rat gastric mucosal cell line RGM-1, to examine the possibility that rHuEPO might directly stimulate the growth of gastric mucosal cells in vitro. Our results show that rHuEPO dose-dependently increased [3H]thymidine incorporation into RGM-1 cells and their expression of c-myc gene. In addition, 125I-rHuEPO specifically bound to RGM-1 cells, and moreover, erythropoietin receptor gene expression was detected by RT-PCR. We conclude that rHuEPO has a direct growth-promoting effect on RGM-1 cells, suggesting possible usefulness of rHuEPO administration for the treatment of gastric mucosal damage in patients with chronic renal failure.