OBJECTIVE Although fat malabsorption in the short-bowel syndrome is caused in part by decreased bile acid secretion, bile acid replacement therapy is not used because of the belief that ingested bile acids would worsen diarrhea, outweighing the benefits of improved fat absorption. This study compared the effect of a natural conjugated bile acid mixture from ox bile with that of cholylsarcosine, a synthetic conjugated bile acid, on fat absorption and diarrhea in a patient with the short-bowel syndrome. Cholylsarcosine is resistant to bacterial metabolism and has no cathartic activity. METHODS Metabolic balance studies and a clinical trial were performed in an emaciated patient with the short-bowel syndrome and ileostomy in whom parenteral nutrition could not be used. RESULTS In balance studies, conjugated bile acid replacement therapy with either preparation caused fat absorption to increase by approximately 40 g/day. Calcium absorption also increased. Neither bile acid product caused a clinically significant increase in ileostomy water output. During a 4-month outpatient trial, while the patient ingested 2 g/meal natural bile acids, her weight increased from 80 to 98 lb, without side effects. CONCLUSIONS Conjugated bile acid replacement therapy should be part of the armamentarium for the treatment of selected patients with the short-bowel syndrome.