We have studied the dissolution rate of radiolucent gallstones from validated measurements of gallstone area derived from standardized oral cholecystography in 48 patients receiving chenodeoxycholic (chenic) acid, 15 mg/kg/day. Patients were matched in pairs according to gallstone size and randomly allocated to one of two treatment groups. Group A was given chenic acid in three divided doses at mealtimes with an unrestricted diet (the conventional regimen), and group B was given bedtime chenic acid with a low cholesterol diet. In the 24 matched pairs, the mean reduction in gallstone area at 6 months on regimen A was 36% and on B 60%. Median reductions in area were 20% and 57%, respectively (P less than 0.02). Of these matched pairs, 20 were followed at 6 month intervals for 42 months. There was a significant correlation between percentage reduction in gallstone area at 6 months and length of treatment necessary for complete dissolution (P less than 0.001). Fifty percent achieved complete dissolution by 30 months on regimen A, and by 12 months on regimen B (NS). We conclude that gallstone dissolution rate during chenic acid treatment is approximately doubled by bedtime administration plus a low cholesterol diet, thus reducing the duration and cost of treatment.