Epidemiological and experimental evidence have shown that nicotine has harmful effects on the gastric mucosa. The mechanisms by which cigarette smoking or nicotine adversely affect the gastric mucosa have not been fully elucidated. In this report, clinical and experimental data are reviewed. The effects of nicotine from smoking on gastric aggressive or defensive factors are discussed. Nicotine potentiates gastric aggressive factors and attenuates defensive factors; it also increases acid and pepsin secretions, gastric motility, duodenogastric reflux of bile salts, the risk of Helicobacter pylori infection, levels of free radicals, and platelet-activating factor, endothelin generation, and vasopressin secretion. Additionally, nicotine impairs the therapeutic effect of H2-receptor antagonists and decreases prostaglandin synthesis, gastric mucosal blood flow, mucus secretion, and epidermal growth factor secretion. Although many of the studies provide conflicting results, the bulk of the evidence supports the hypothesis that nicotine is harmful to the gastric mucosa.