The object of this investigation was to determine gallstone susceptibility to laser lithotripsy and to discover whether this susceptibility is related to the computed tomography (CT) appearance of gallstones. Gallstones collected from surgery were scanned by CT and classified as homogeneously dense (greater than 90 Hounsfield units [HU]), homogeneously faint (30-60 HU), or rimmed. Sixty stones were subjected to laser energy at 20, 40, 60, 80, or 100 mJ. Fracture and fragmentation (all particles less than 2 mm) were assessed in relation to the energy level setting and number of laser pulses delivered. The authors found that a 480-nm, flashlamp-pumped pulsed dye laser can fragment completely all the types of human gallstones that were tested, although there is significant variability in gallstone susceptibility to laser lithotripsy. This susceptibility varies with CT appearance: dense stones require fewer pulses and lower energies for fracture and fragmentation, compared to faint or rimmed stones. The authors anticipate that CT characterization of gallstones may be a clinically useful screening tool before laser lithotripsy.