In our previous studies of cirrhotic subjects lactulose caused a 25% decrease in the urea production rate associated with a decrease in urinary urea excretion and an increase in stool nitrogen. The decrease in the rate of urea production was an indirect measure of reduction in gut ammonia production. The present study was designed to determined if the poorly adsorbed antibiotic neomycin had an additive effect in reducing ammonia production when administered in combination with lactulose. Six stable cirrhotic subjects received isonitrogenous diets during separate lactulose and lactulose + neomycin treatment periods. The addition of neomycin to a lactulose regimen caused a 17% reduction in the urea production rate that was quantitatively accounted for by a 70% reduction in the urea degradation rate. The intestinal urea clearance rate demonstrated a parallel reduction, indicating an inhibition of bacterial ureolysis. There was no evidence that neomycin altered the effects of lactulose since urinary urea excretion did not rise, fecal nitrogen remained high, and stools remained acidic. These results demonstrate that neomycin inhibited bacterial ureolysis when administered with lactulose while lactulose itself was metabolized and its individual effect on nitrogen metabolism persisted. Lactulose and neomycin, when administered together, had an additive effect in reducing gut ammonia production in cirrhotic subjects.