The effect of a tablet containing the antiflatulent, simethicone, on intestinal hydrogen (H2) elimination in breath was studied. In three trials, normal subjects (age 12-52 years) received, on subsequent days, lactulose or lactulose with two tablets of either simethicone or placebo in randomized order. Breath samples were collected over 210 min and analyzed by gas chromatography for H2. The time course of H2 expiration above baseline levels was calculated and compared for the three tests. No significant differences in transit time were found. Cumulative H2 expiration was significantly lower after simethicone compared to placebo. H2 production from stool incubated with simethicone or placebo indicated that the drug had no effect in reducing the fermentative production of H2 in vitro. Interestingly, the vehicle present in the tablets could be fermented by intestinal bacteria. Simethicone reduced the amount of H2 eliminated in breath, but this effect was offset partially by H2 production from the fermentation of unabsorbable substances used in the formulation of the tablets.