This study was performed to evaluate the risk of gallstone formation during long-term treatment with the long-acting somatostatin analog octreotide (SMS 201-995). Twelve patients (8 men, 4 women--mean age 43 years) treated with continuous subcutaneous octreotide infusion for acromegaly (mean duration 26.5 months, mean dose 541 micrograms/day) were included. Bile collection by duodenal intubation was performed before, during, and 45 days after octreotide treatment in 3, 12, and 8 patients, respectively. Abdominal ultrasonography and/or oral cholecystrography were also performed before (n = 9 patients), during (n = 12), and after treatment (n = 10). Bile examination was normal in the 3 patients controlled before treatment but showed that 58.3 percent of the treated patients had cholesterol monohydrate crystals. After discontinuation of octreotide only 25 percent of patients had cholesterol crystals. In 3 patients (25 percent) treated longer than 6 months, cholesterol crystals occurred prior to the occurrence of small radiolucent gallstones: one patient underwent cholecystectomy because of biliary colic, while in the two others, complete dissolution of stones was obtained after 10 months of treatment with ursodeoxycholic acid given in association with octreotide. None of the 9 other acromegalic patients (including 7 treated more than 20 months) developed stones. Cholesterol gallstone formation seems to be increased in acromegalic patients during long-term octreotide treatment but the exact incidence remains to be determined in larger series of patients.