The in vivo response to short-pulsed Nd-YAG laser damage to the trabecular meshwork has not been studied in the human eye. The nature of the response will determine the potential efficacy of this treatment for glaucoma. We have investigated short-pulsed laser trabeculotomy lesions created in the trabecular meshwork of four human eyes within 18 hr prior to enucleation for intraocular melanoma. Scanning electron micrographs showed irregular craters (150-300 micron diameter) in the trabecular meshwork surrounded by trabecular beams which were splayed towards the anterior chamber. The adjacent damage to trabecular and corneal tissues was characterized by denudation of endothelial cells and deposition of debris. Light and transmission electron micrographs of the edge of the trabeculotomy lesions revealed fragmentation of the endothelial cells and splitting of the trabecular beams. Preservation of normal morphology was noted in the deeper tissues within 50 micron of the edge of the crater. Neutrophils were present within 20 min of laser treatment whilst macrophages characterised the inflammatory response at later stages. Perforation of the canal of Schlemm was only obtained with lesions in the middle of the trabecular meshwork but not with lesions placed more anteriorly.