The recent description of the synthesis of nitric oxide (NO) in vivo and its putative role in endothelial-dependent vasodilatation has led to considerable interest in possible roles for the molecule. In this study the distribution, origin and some aspects of the physiology of NO found in the cerebral circulation is examined. A rich supply of nerve fibres displaying immunoreactivity against nitric oxide synthase (NOS) could be seen in the adventitia of the cat cerebral vessels. There was a large number of NOS-positive cells in the sphenopalatine ganglion and these constituted a sub-population of the vasoactive intestinal polypeptide (VIP) positive cells. Blockade of NOS activity with NG-nitro-L-arginine methyl ester (L-NAME) significantly attenuated the cerebral vasodilator response to facial nerve stimulation when applied locally to the cortex. Intravenous administration of L-NAME did not affect the VII-elicited cerebral vasodilator response. It may be concluded that the parasympathetic nerves innervating the cerebral circulation contain NOS and furthermore, since blockade of NOS reduces parasympathetic vasodilatation, that NO is one of the transmitters in this system.