CO2 gas has been proposed as a new perfusion medium for laser angioplasty. To compare CO2 gas with conventional saline perfusion, 146 fresh specimens of normal and atheromatous human artery were irradiated with a neodymium: yttrium-aluminum-garnet laser with a sapphire probe in flowing whole blood in an experimental circulation-occlusion model. The dimensions of the ablation crater and the extent of the surrounding tissue damage were measured microscopically. Significantly better ablation of atheromatous plaque was achieved with CO2 perfusion than with saline perfusion: mean ablation areas were 5.0 mm2 versus 2.8 mm2, respectively (P = .001, Student t test). In contrast, the ablation areas on normal vessel wall were identical (mean, 3.4 mm2) with the two perfusion media. Moreover, CO2 gas functioned as a negative contrast agent and facilitated direct monitoring of the laser recanalization procedure. On an experimental basis, CO2 gas perfusion seems to improve the efficiency and safety of laser ablation in human arteries.