The ability of chenodeoxycholic acid to dissolve gallstones was compared using different dosage regimens in two groups of 21 patients. The groups were closely matched for patient factors and stone characteristics known to influence the outcome of dissolution treatment. The patients in one group received a standard dose of chenodeoxycholic acid (15 mg/kg/day) taken at mealtimes. The patients in the second group received a bedtime dose of chenodeoxycholic acid which was sufficient to result in a proportion of this bile acid of 70% in the bile acid pool. This dose was monitored using serum bile acid profiles and varied within this test group (range 5.1–13.9 mg/kg/day). The number of patients whose stones completely dissolved in 12 months was similar in the standard-dose (7 of 21) and monitored-dose (8 of 21) groups. These results suggest that a bedtime dose of chenodeoxycholic acid, which is monitored to produce a level of 70% chenodeoxycholic acid in the biliary bile acid pool, is lower than the standard dose taken after meals but is of comparable efficacy. Lower dosage has the advantage of reducing costs and side effects from the drug, although serum bile acid profiling increases the cost of treatment.