Neuropeptide Y (NPY) immunoreactivity (-IR) was found to be present in perivascular nerves in the cat dental pulp and oral mucosa. Many ganglion cells in the superior cervical ganglion also contained NPY-IR. Ligation of the inferior alveolar or lingual nerves produced an accumulation of NPY-IR in axons proximal to the site of ligation, suggesting an anterograde axonal transport of the peptide. After unilateral sympathectomy the NPY-IR disappeared in the dental pulp and oral mucosa on the ipsilateral side. Reversed phase high performance liquid chromatography showed that the main peak of NPY-like immunoreactivity found in the superior cervical ganglion co-chromatographed with synthetic porcine NPY. Changes in blood flow in dental pulp or oral mucosa were measured indirectly by recording local clearance of 125I during electrical stimulation of the sympathetic nerve or during close intra-arterial infusion of noradrenaline or NPY. All three procedures resulted in a pronounced decrease in local blood flow of a similar magnitude in both tissues. After alpha-adrenoceptor blockade with phentolamine, the vasoconstrictor effect of noradrenaline was abolished. However, the effect of sympathetic stimulation after phentolamine was only partially reduced (23-54%) and the response to NPY was almost unaffected by the alpha-receptor blockade. The remaining effect of sympathetic stimulation after phentolamine was abolished by guanethidine. However, the response to NPY was not changed by the latter drug. In conclusion, the vasoconstrictor response in the dental pulp and oral mucosa caused by activation of sympathetic nerves is more resistant to phentolamine than the response induced by infusion of exogenous noradrenaline. Since NPY is probably co-localized with noradrenaline in the sympathetic perivascular nerves and NPY reduces local blood flow, it is proposed that this peptide is involved in sympathetic vascular control in oral tissues.