Recent use of the cholelitholytic agent, methyl tertiary butyl ether (MTBE) has demonstrated its efficacy in the dissolution of cholesterol calculi. In three patients with retained stones in the bile duct, MTBE was instilled and aspirated through a T tube to effect dissolution. Stones dissolved completely in two patients, while in the third, partial dissolution permitted instrumental extraction through the T tube tract. In this third patient, dissolution of gallbladder stones in vitro was relatively slow. Patients tolerated the procedure well and there were no major complications. There was no evidence of duodenal inflammation in two patients who underwent duodenoscopy and biopsy before and after treatment. Four patients with cholesterol cholelithiasis underwent direct gallbladder perfusion with MTBE. The mean size of the gallstones was 0.8 cm (range 0.25-1.75 cm) and the mean number of stones per patient was four (range 1-13 stones). MTBE was instilled via a percutaneous gallbladder catheter inserted under local anesthesia with X-ray control. In three patients, the stone dissolution appeared to be complete after three to six hours of treatment. In the fourth patient, catheter displacement led to termination of dissolution therapy. Follow-up ultrasonograms in two patients demonstrated residual debris not visualised on the immediate post-dissolution films. Complications occurred in two patients and included catheter dislodgement and bile leakage after catheter withdrawal. Biliary perfusion with MTBE is a therapeutic option in patients with retained stones in whom instrumental retrieval has failed. It may also have a role in selected patients with symptomatic stones in the gallbladder.