Human gallstones were surgically implanted in the gallbladders of 14 pigs. Nine to 16 days later a sheath was successfully placed percutaneously into the gallbladders of 13 animals using ultrasound and fluoroscopy. Two methods were used to guide laser fragmentation: (1) fluoroscopy and a steerable double lumen catheter (two animals), and (2) a flexible endoscope (11 animals). Laser treatment was done in 12 animals with a flashlamp-pumped pulsed-dye laser. A mean of 3600 pulses/animal were delivered using a wavelength of 504 nm and a maximum energy of 60 mJ/pulse. No fragmentation occurred in two animals, partial fragmentation occurred in six, and complete fragmentation occurred in four. Endoscopic guidance was superior to fluoroscopic guidance. Complications (sheath dislodgment, gallbladder perforation, bleeding) occurred in eight of 14 animals. Pulsed-dye laser fragmentation of gallbladder stones is feasible using endoscopic guidance. The use of this technique through an acute percutaneous tract may be associated with complications.