Information from histopathologic examination of coronary arterial atherosclerotic plaques treated with in vivo laser energy is sparse. Directional atherectomy provides biopsies for study of tissue changes (injury) due to coronary arterial debulking devices, including laser. Sixteen patients who presented with acute ischemic coronary syndromes underwent debulking of a total of 17 obstructive intracoronary lesions with pulsed-wave holmium:YAG laser (2.1 microm wavelength). Laser was performed with the "pulse and retreat" technique which incorporates slow catheter advancement (0.5-1 mm/s) with controlled emission of energy. Immediately postlasing, directional atherectomy was utilized to obtain irradiated plaque tissue for pathologic examination. Extent of laser-induced tissue injury to plaques was graded as 0 (no tissue damage), 1 (small foci or charring and vacuoles), 2 (large amount of charring, edge disruption and vacuoles) and 3 (extensive tissue damage). Angiographically and clinically, all 17 lesions were successfully debulked with the laser energy (mean 47+/-25 pulses), with a reduction of target lesion percent diameter stenosis from 92+/-6% to 47+/-25%. Adjunct balloon dilations further reduced the target lesions to a final of 10+/-10% stenosis. The histopathologic examination of the lased specimens demonstrated that 13 lesions (76%) had no evidence of laser-induced injury (Grade 0). Four lesions had low-level injury (Grade 1), and none had evidence of Grade 2 or 3 laser-induced trauma. Therefore, a laser debulking technique, which incorporates slow catheter advancement with controlled emission of pulses, does not cause significant injurious effects to the irradiated plaque.