Capsaicin, the active ingredient in chili, has been implicated as both a cytoprotective and a detrimental agent to the gastric mucosa. The effect of capsaicin on Helicobacter pylori has not been investigated previously. Therefore, we performed in vitro time- and concentration-dependent studies to examine the growth of H. pylori in the presence of capsaicin. Capsaicin specifically inhibited growth of H. pylori dose-dependently at concentrations greater than 10 micrograms ml-1 (P < 0.05) but did not inhibit the growth of a human fecal commensal Escherichia coli strain. Bactericidal activity was observed within 4 h. Capsaicin continued to exhibit bactericidal activity when incubated at pH values as low as 5.4. Ingestion of chili, therefore, could have a protective effect against H. pylori-associated gastroduodenal disease. This effect deserves further study in animal models.