Sigma ( σ ) recognition sites are a unique class of binding sites, distributed in the nervous system and in peripheral organs acting as receptors for some unidentified endogenous ligand.They bind an array of structural classes of compounds including haloperidol and (+)-benzomorphans, such as (+)-pentazocine. We are investigating their role in the regulation of autonomic functions since they may interfere with neurotransmitter release, modulating their action on innervated tissue. We found distinguishable populations of sites in the rabbit iris-ciliary body and evaluating their contribution in the regulation of intraocular pressure in the rabbit. In vivo findings are completed by in vitro analysis of their role on electrically stimulated release of [3H]NE from postganglionic sympathetic neurons and on isoproterenol-induced cAMP accumulation in isolated iris-ciliary body. These findings may prove a contribution of sigma ligands in the control of ocular hypertension.