Three bismuth compounds (tripotassium dicitrate bismuthate, bismuth subsalicylate, and bismuth subnitrate) were tested in vitro and in vivo for their effect on fermentation by colonic bacteria. The studies in vitro were done with use of a technique designed to determine the effect of each one of the bismuth compounds on the fermentation of several stool samples that had been mixed with lactose as additional fermentable substrate (fermentation of lactose-enriched stools, FLES). The three bismuth compounds reduced FLES significantly in 47 (81%) of 58 of the stool samples used to test their effect. Bismuth subsalicylate, which reduced FLES in 10 of 10 stool samples, showed the greatest reduction (mean reduction, 74%; P<.0001). The in vivo studies, done in six flatulent patients, showed significant reduction (P <.01) of colonic fermentation of ingested raffinose by oral bismuth subnitrate given for 8 days.