The Neodymium (Nd):YAG laser is commonly used in ophthalmology mainly for the posterior capsulotomy in patients with secondary cataract after extracapsular cataract extraction. A frequent side-effect following different kinds of YAG laser treatments is an acute increase in the intraocular pressure (IOP). The present study addresses the role of calcitonin gene-related peptide (CGRP) in the ocular irritative response following YAG laser anterior capsulotomy in rabbits. The YAG laser anterior capsulotomy caused an irritative response in the eye, which consisted of an increase in the IOP, miosis and breakdown of the blood-aqueous barrier. Following YAG laser capsulotomy, CGRP-immunoreactivity was found in the aqueous humour in different molecular weight forms as revealed by gel-permeation chromatography. One of the peaks coeluted with synthetic human CGRP. Methysergide attenuated the increase in the IOP and disruption of the blood-aqueous barrier, but not the miosis, following YAG laser anterior capsulotomy. The present study demonstrates the release of CGRP into the aqueous humour following YAG laser capsulotomy, and suggests that CGRP is partly causing the increase in IOP and disruption of the blood-aqueous barrier in this irritative response.