The results of bile salt treatment in patients with radiolucent stones and a functioning gall bladder have been poor. In 42 of these patients awaiting cholecystectomy we determined the value of duodenal bile examination in predicting gall stone composition, and thus identifying those less likely to respond to bile salt therapy. Based on chemical analysis and scanning electron microscopy, 28 of 42 (67%) gall stones retrieved at surgery were potentially insoluble. Microscopic examination of duodenal bile correctly identified 21 (75%) of them: it predicted all four (100%) pigment stones, three of six (50%) calcium carbonate containing cholesterol stones, and 14 of 18 (78%) cholesterol stones with pigment shells. It was nearly as reliable as microscopic examination of bile aspirated directly from the gall bladder during surgery (21 (75%) v 23 (82%); p = NS). Furthermore, the presence of cholesterol crystals in duodenal bile was a more sensitive indicator than chemical detection of supersaturation (34 of 38 (89%) v 25 of 35 (71%); p < 0.05) for prediction of cholesterol gall stones. Microscopic examination of duodenal bile, if used as a screening test, could help to exclude potential non-responders and thereby improve considerably the results of oral bile salt treatment for gall stone dissolution.