Background: Leptin is a small 16 kD protein that is secreted by adipocytes and is known to influence food intake and energy expenditure. Leptin has also been shown to stimulate cell proliferation as well as inhibit programmed cell death (apoptosis) in some cells. Both leptin and the leptin receptor (Ob-R) have been found in the stomach. However, the role of leptin on the proliferation of normal human gastric mucous epithelial cells is not known. The purpose of the present study was to examine the role of leptin on normal gastric mucosal cell growth. Methods: Normal human gastric mucous epithelial cells were plated in multiwell plastic dishes and grown using standard cell culture techniques. Wild-type H. pylori (60190) were grown on chocolate agar plates. RT-PCR was used to detect the Ob-R in gastric cells. The MTT-assay was used to measure cell growth. The Hoechst-dye binding assay was used to measure apoptosis. Results: The Ob-R was detected in normal human gastric mucous epithelial cells using PCR primers that detected all Ob-R forms. Leptin alone (10-100nM) had no effect on normal gastric mucosal cell proliferation. Leptin (10-100nM) had no effect on 4nM or 8nM (25ng/ml or 50ng/ml) epidermal growth factor-stimulated normal gastric cell proliferation. Leptin (25nM, 50nM, 100nM) dose-dependently reduced camptothecin-induced apoptosis in normal gastric cells by 14%, 38%, 48%, respectively. Leptin (100nM) reduced H.pylori-induced apoptosis by ~86% in gastric cells. Neither the vehicle control for camptothecin (DMSO) or leptin (acid/base mixture) had any effect on gastric cell apoptosis. Conclusions: The data suggest that leptin does not directly stimulate the proliferation of normal human gastric mucosal cells, but instead may prolong gastric cell life by regulating apoptosis.