During the National Cooperative Gallstone Study, therapy with chenodiol, 750 or 375 mg/d, for 2 years resulted in confirmed, complete gallstone dissolution in 14% and 5% of patients, respectively, and partial dissolution (greater than 50%) in 27% and 18%. The present study was done to determine the frequency with which complete dissolution occurs in patients having partial dissolution of gallstones who receive additional therapy. Eighty-six of one hundred thirty-eight eligible patients continued to receive 750 mg/d (61 patients) or 375 mg/d (25 patients) of chenodiol for 1 year. Patients whose oral cholecystogram at the end of the year showed further (greater than 50%) dissolution continued to receive chenodiol, (28 patients at 750 mg/d and 11 patients at 375 mg/d) for a second year (total duration of therapy, 4 years). A final oral cholecystogram was taken at the end of the fourth year. Complete dissolution occurred in 23% and 16% of patients receiving chenodiol, 750 or 375 mg/d, respectively, for an additional 1 or 2 years.