Lactulose, a synthetic disaccharide, which is neither absorbed nor metabolized in the upper intestinal tract of normal man, is degraded by bacteria in the intestinal tract with the production of acidified bowel contents. This agent appears to be effective therapy in chronic portalsystemic encephalopathy but has not been studied in acute hepatic encephalopathy. In preliminary uncontrolled studies we have treated 24 episodes of acute nitrogenous hepatic coma with lactulose and compared our results to 24 retrospectively matched episodes of encephalopathy treated with neomycin. The two groups were similar in type, severity, and laboratory features of the disease. Lactulose was administered in doses of 100 to 200 ml/day, usually following a large loading dose which functions as a cathartic. Neomycin dosage ranged from 3 to 12 gm daily.Lactulose effectively reversed the coma in 20 of the 24 episodes (83 per cent). Neomycin was effective treatment in 23 of the 24 episodes (96 per cent). This difference was not statistically significant. Improvement in arterial ammonia levels, in electroencephalograms, and in other measures of encephalopathy was similar in the two groups. Recovery from encephalopathy appeared slightly faster with lactulose than with neomycin but such a difference between nonrandomized groups is of doubtful clinical importance. Prospective randomized controlled trials of lactulose in acute hepatic encephalopathy are required to establish the efficacy of this form of therapy.