The pharmacological profile and the anatomical localization of beta-adrenergic and muscarinic cholinergic receptors of the vasa nervorum were studied in sections of sciatic nerve using radioreceptor binding and light microscope autoradiography techniques. Sprague-Dawley rats of 4 and 24 months of age were used. [3H]Dihydroalprenolol (DHA) and [3H]quinuclidinyl benzilate (QNB) were used to label beta-adrenergic and muscarinic cholinergic receptors, respectively. The ligands were bound to sections of rat sciatic nerve in a manner consistent with the labelling of beta-adrenergic or muscarinic cholinergic receptors in the 2 age groups investigated. The dissociation constant (Kd) values (about 1.37 nM for [3H]DHA and 0.75 nM for [3H]QNB) did not significantly change between 4- and 24-month-old rats. The maximum concentration of binding sites (Bmax) for [3H]DHA was decreased by about 35% in 24 in comparison with 4-month-old rats. The Bmax value for [3H]QNB was reduced by about 50% in the aged rats. Light microscope autoradiography revealed the development of specific silver grains in the medial layer of epineurial and perineurial arteries in sections of sciatic nerve exposed either to [3H]DHA or [3H]QNB. The number of silver grains developed in epineurial and perineurial arteries of rats of 24 months is significantly lower than in animals of 4 months. The above results suggest the occurrence of an age-dependent loss in the density of beta-adrenergic and muscarinic cholinergic receptors of vasa nervorum. Vasa nervorum are the blood vessels which supply peripheral nerve trunks. They are constituted by outer (epineurial) and inner (perineurial) arteries and veins as well as by a capillary (endoneurial) plexus. Vasa nervorum are innervated by both sympathetic and non-sympathetic nerves which probably play a role in the pathogenesis of some neuropathies. Several different neurotransmitter containing nerve fibres have been identified in the vasa nervorum perivascular plexuses. However, no information is so far available concerning the neurotransmitter receptors of vasa nervorum. Moreover, although the occurrence of age-dependent changes in peripheral nerve morphology and function is well documented, very few reports were centered on the age-dependent changes of the vasa nervorum. The aims of the present study were to characterize pharmacologically and to localize anatomically the beta-adrenergic and muscarinic cholinergic receptors in the rat vasa nervorum. Moreover, the effect of ageing on the density and pattern of these receptors was investigated.