Epidermal growth factor (EGF) and heparin-binding EGF-like growth factor (HB-EGF) exert their activities through the same cell surface receptor. In the present study, the role of EGF in cell kinetics of rat gastric epithelial cell line, RGM-1, in which HB-EGF is known to function in an autocrine fashion, was investigated. EGF stimulated the mucus glycoprotein synthesis which is characterized with cell maturation, but competed with HB-EGF for cell proliferation. By flow cytometric analysis, EGF inhibited G2/M transition by 48 h after stimulation and induced apoptosis manifested by hypodiploid DNA by 72 h after stimulation. Consistent with this, DNA ladder formation together with the histone-associated DNA fragments was found in EGF-treated cells. These results indicate that EGF and HB-EGF possess different functions in RGM-1 cells and that EGF acts as a mediator of both cell maturation and apoptosis in these cells.