To better define a minimal but optimal dose of oral neomycin to suppress ammonia production by bowel flora, several dosage regimens were examined in normal healthy volunteers. Fecal urease activity was quantitatively determined and was used as an indirect measure of intrinsic ammonia production by bowel flora. Large doses of neomycin were found to exert inhibition of fecal urease for many days. There was considerable variation in enzymatic activity among subjects even after adjustments were made for protein content of the stool. Depending on the dose, there was a 1- to 3-day lag in neomycin effect on stool urease activity and several days of continued effect. The most effective regimen of those studied was a loading dose of 6 g of neomycin given in three divided doses on day 1, followed by 1 g twice daily.