Biliary stones can be removed in 85% to 90% of patients using endoscopic sphincterotomy; in the rest alternative methods are required. Thirty-eight consecutive patients in whom conventional methods had failed underwent laser lithotripsy with a new laser system. A flashlamp-pumped pulsed laser with rhodamine 6G as dye (594 nm) has a tissue-stone recognition system that can identify bile duct stones by analyzing backscattered light and interrupt the pulse in case of tissue contact (Lithognost, Telemit, Munich, Germany). Access of the 0.25- or 0.30-mm-diameter laser fiber to the stones was achieved perorally in 18 patients. In 13 of these cases, eccentrically located stones in the middle or proximal common bile duct were targeted with a 3.4-mm miniscope introduced through a standard duodenoscope. Fluoroscopically guided peroral lithotripsy was performed in 5 patients with stones in the distal common bile duct that could be approached with a standard ERCP catheter. Percutaneous cholangioscopic laser lithotripsy was carried out in 20 patients with stones not amenable to retrograde techniques. The mean number of bile duct stones per patient was 3.6, and the average diameter of the largest stone of each patient was 25 mm (range, 8 to 52 mm). The bile ducts were cleared in all but 1 patient in a mean number of 1.3 sessions lasting 15 to 115 minutes (mean, 60). No laser-related complications were observed. The Lithognost laser was successfully used in 37 of 38 patients referred for the removal of difficult bile duct stones.(ABSTRACT TRUNCATED AT 250 WORDS)