AIM: To evaluate the gastro-protectlve effect of capsaicin against the ethanol- and indomethacin (IND)-induced gastric mucosal damage in healthy human subjects. METHODS: The effects of small doses (1-8 μg/mL, 100 mL) of capsaicin on the gastric acid secretion basal acid output (BAO) and its electrolyte concentration, gastric transmucosal potential difference (GTPD), ethanol- (5 mL 300 mL/L i.g.) and IND- (3×25 mg/d) induced gastric mucosal damage were tested in a randomized, prospective study of 84 healthy human subjects. The possible role of desensitization of capsaicin-sensitive afferents was tested by repeated exposures and during a prolonged treatment. RESULTS: Intragastric application of capsaicin decreased the BAO and enhanced “non-parietal” component, GTPD in a dose-dependent manner. The decrease of GTPD evoked by ethanol was inhibited by the capsaicin application, which was reproducible. Gastric microbleeding induced by IND was inhibited by co-administration with capsaicin, but was not influenced by two weeks pretreatment with a daily capsaicin dose of 3x400 μg i.g. CONCLUSION: Capsaicin in low concentration range protects against gastric injuries induced by ethanol or IND, which is attributed to stimulation of the sensory nerve endings. AIM: To evaluate the gastro-protectlve effect of capsaicin against the ethanol- and indomethacin (IND) -induced gastric mucosal damage in healthy human subjects. METHODS: The effects of small doses (1-8 μg / mL, 100 mL) of capsaicin on the gastric acid secretion basal acid output (BAO) and its electrolyte concentration, gastric transmucosal potential difference (GTPD), ethanol- (5 mL 300 mL / L ig) and IND- (3 x 25 mg / were tested in a randomized, prospective study of 84 healthy human subjects. The possible role of desensitization of capsaicin-sensitive afferents was tested by repeated exposures and during a prolonged treatment. RESULTS: Intragastric application of capsaicin decreased the BAO and enhanced "non- The decrease of GTPD evoked by ethanol was inhibited by the capsaicin application, which was reproducible. Gastric microbleeding induced by IND was inhibited by co-administration with capsaicin, but was not influenced by two weeks pretreatment with a daily capsaicin dose of 3x400 μg i.g. CONCLUSION: Capsaicin in low concentration range protects against gastric injuries induced by ethanol or IND, which is attributed to stimulation of the sensory nerve endings.