The suitability of a pulsed dye laser (504 nm) in experimental and clinical angioplasty was investigated. In an experimental study, the ablation thresholds were 3 J/cm2 +/- 8 (mean +/- standard deviation) for fibrofatty plaque and 25 J/cm2 for calcified tissues under saline. At a radiant exposure of 10 J/cm2 the etch rates were 1.7 microns per pulse +/- 0.3 for media, 2.8 microns/pulse +/- 0.4 for normal intima, and 3.9 microns/pulse +/- 1.1 for fibrofatty plaque (P less than .05). Pressure wave effects with a separation of tissue layers were predominantly localized at the internal elastic lamina. Thermal injury with vacuolations extended 15 microns +/- 6 into adjacent tissue. For clinical study, laser-assisted balloon angioplasty was performed in 10 patients (64 years +/- 14) with occlusions of peripheral arteries using a 9-F multifiber ring catheter. Lesion length ranged from 2 to 12 cm (mean, 7 cm). Laser angioplasty with an 80 mJ/pulse decreased the mean stenosis from 100% to 58% +/- 12% (P less than .005). The ankle-brachial index rose from a median of 0.48 to 0.88 (P less than .001). In 33% of patients, there were subintimal dissections after laser angioplasty. After a mean follow-up of 10.2 months, the overall clinical success was 70% with a primary patency of 78%. The over-the-wire approach with a pulsed dye laser may constitute a safe and feasible tool in laser angioplasty.