BACKGROUND The growth and development of the fetal gastrointestinal tract is likely mediated, in part, by peptide growth factors. We compared the mitogenic effects of graded doses of hepatocyte growth factor (HGF) to epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and insulin-like growth factor-1 (IGF-1) on fetal rabbit gastric epithelial cells. METHODS Fetal rabbit gastric epithelial cells were purified by mechanical dissociation and selected culture and grown in short-term (24 h) and long-term (12 days) culture. Stimulation of fetal gastric epithelial cell growth in response to individual peptide growth factors was measured by [3H]thymidine incorporation and cell counting. RESULTS In short-term culture, HGF stimulated [3H]thymidine incorporation in a dose-dependent manner from a threshold at 10 pM to a maximum at 100 pM. For EGF and TGF-alpha, maximal stimulation occurred at 100 pM. For HGF, maximal [3H]thymidine incorporation was 3.6 +/- 0.7 times basal. For EGF and TGF-alpha, maximal [3H]thymidine incorporation was 4.3 +/- 0.4, and 3.6 +/- 0.4 times basal, respectively. For IGF-1, maximal [3H]thymidine incorporation was only 70% of the maximal effect observed for the other growth factors tested. Rabbit amniotic fluid increased [3H]thymidine uptake in a dose-dependent manner. In long-term culture, purification to greater than 90% epithelial cells was attained after 12 days treatment. For HGF, EGF, TGF-alpha, and 20% rabbit amniotic fluid, significant increases in cell number above control (P < 0.05) were observed at 1 nM concentrations. None of these individual factors, however, increased cell growth as significantly as that of 10% fetal bovine serum. CONCLUSIONS Our results suggest that: (1) HGF stimulates [3H]thymidine uptake and cell proliferation in fetal rabbit gastric epithelial cells in vitro, and (2) HGF's mitogenic effect on fetal rabbit gastric epithelial cell growth is comparable to that observed for EGF and TGF-alpha, but superior to the effect observed for IGF-1.