BACKGROUND Previous in vitro studies demonstrated that during excimer laser ablation of aortic tissue in saline, a fast-expanding and imploding vapor bubble is formed. The present in vivo study was designed to demonstrate the formation of a fast-expanding intraluminal bubble in flowing blood and to assess any damage to the adjacent arterial wall. RESULTS Excimer laser pulses (one to 10, at 55 mJ/mm2 per pulse) were delivered coaxially in the femoral and iliac arteries of nine normal rabbits. Time-resolved flash photography of dissected arteries in situ demonstrated a 50% diameter increase within 75 microseconds after the laser pulse and a subsequent invagination (150-500 microseconds) that corresponded with the temporal course of the bubble expansion (up to 3.2 mm in diameter) and implosion observed in a hemoglobin solution. One day after laser light delivery, light microscopy (47 arterial segments) showed abrasion of the internal elastic lamina, medial necrosis, and extensive dissection planes filled with red blood cells. The degree (up to 100% medial necrosis) and extent of damage (up to 1.9 mm in length) increased with the number of delivered laser pulses. CONCLUSIONS In blood, each excimer laser pulse generated a fast-expanding and imploding vapor bubble. In vivo, the intraluminal vapor bubble produced microsecond dilation and invagination of the adjacent arterial segment, which induced dissections and extensive wall damage far beyond the penetration depth of 308-nm laser light (< 100 microns). This unique pattern of extensive wall damage observed in the rabbit might explain the mechanism of dissection observed in humans and might have an impact on the acute and chronic outcome after excimer laser coronary angioplasty.