Abstract To determine the optimum bile acid regimen for rapid gail stone dissolution, 48 gall stone patients were divided into four groups of 12 according to stone diameter and were randomly allocated to receive one of four treatment regimens: bedtime or mealtime chenodeoxycholic acid (CDCA, 12 mg/kg/day) and bedtime or mealtime ursodeoxycholic acid (UDCA, 12 mg/kg/day). An additional 10 patients treated with a combination of CDCA plus UDCA(each 6 mg/kg/day) at bedtime were matched with the 10 patients on bedtime CDCA and the 10 on bedtime UDCA. The gall stone dissolution rates at six and 12 months were determined by standardised oral cholecystography and expressed as the percentage reduction in the gall stone volume after treatment. The gall stone dissolution rate at six months was higher for UDCA than CDCA treatment (median 78% v 48%, p<001), and for bedtime than mealtime administration (69% v 39%, p<002). Both differences were greater for stones <8 mm diameter. The dissolution rate was faster for combination therapy than for CDCA alone at both six (82% v 36%, p<0O05) and 12 months (100% v 54%, p<005), but was not different from UDCA alone. We conclude that bile acid treatment should be confined to patients with smail gail stones and that bedtime administration of combined UDCA and CDCA is likely to provide the most effective and safe combination.