BACKGROUND Fat malabsorption in the short-bowel syndrome (SBS) may in part be caused by decreased bile secretion. Cholylsarcosine is a synthetic conjugated bile acid resistant to bacterial degradation with no cathartic activity. METHODS Metabolic balance studies were performed in four patients with SBS, two with a colon and two with a jejunostomy. RESULTS Treatment with cholylsarcosine, 6 and 12 g/day, increased fat absorption by 17 +/- 3 g/day (0.7 MJ/day; P <0.05) and 20+/-1 g/day (0.8 MJ/day; P <0.001; mean +/- standard error), respectively, to a total absorption of energy from fat of 2.0-2.2 MJ/day. Total absorption of energy increased from 11.0 MJ/day to 11.7 MJ/day (bomb calorimetry). Energy absorbed from carbohydrates (6.5 MJ/day) did not change. Faecal output increased in one of the patients with a colon and was unchanged in the other three patients. A higher percentage of the medium-chain and the unsaturated fatty acids were absorbed in comparison with the long-chain and the saturated fatty acids (100% of C8:0, 92% of C10:0, 74% of C12:0, 52% of C14:0, 30% of C16:0, 16% of C18:0, and 47% of unsaturated C18 fatty acids). Treatment with cholylsarcosine increased absorption of C14:0 by 23%-29%, of C16:0 by 59%-74%, of C18:0 by 125%-138%, and of unsaturated C18-fatty acids by 36%-45%. A fifth patient (without a colon) was enrolled in the study but had to be excluded because cholylsarcosine, 6 g/day, resulted in nausea and anorexia. CONCLUSIONS Cholylsarcosine increased fat absorption in SBS. The effect was relatively more pronounced on absorption of the low-absorbable, longer-chained, and saturated fatty acids. The overall gain in absorption of energy was small (6%) because energy absorption from carbohydrates was threefold higher than that from fat. Cholylsarcosine may have cathartic effects on some SBS patients with a colon. The maximal efficacy of cholylsarcosine was reached at a dose of 6 g/day, compared with 12 g/day in three of four patients.