The significance of neuropeptide Y (NPY) in the cerebral circulation has been examined in the rat using immunocytochemistry, isolated cerebral artery preparations, and quantitative autoradiographic techniques for determining local CBF and glucose utilisation. In the rat the middle cerebral artery and the lenticulostriate artery from which blood is supplied to the caudate nucleus were found to be invested with numerous perivascular NPY immunoreactive nerve fibres. NPY (3-300 nM) contracted rat middle cerebral artery segments in a concentration-dependent manner. Intracerebral microinjections of NPY (200 pmol) or vehicle (1 microliter) were performed in rats after full recovery from anaesthesia via previously implanted guide cannulae. Following injection of NPY into the striatum, local blood flow was markedly decreased by 36% throughout the ipsilateral caudate nucleus (e.g., from 104 +/- 25 to 67 +/- 15 ml 100 g-1 min-1; mean +/- SD), whereas glucose use in this region was not altered significantly (e.g., 73 +/- 8 and 74 +/- 10 mumol 100 g-1 min-1 with vehicle and NPY, respectively). Intrastriatal NPY did not alter CBF or glucose use in the majority of other brain areas, including all of the 40 contralateral regions examined and almost all regions within the ipsilateral hemisphere. In a small number of highly discrete brain areas remote from the injection site (e.g., amygdala), there were significant reductions in blood flow with minimal changes in glucose use. Since NPY is present around rat cerebral blood vessels, is capable of evoking their contraction, and has the ability to produce reductions in blood flow independently of oxidative metabolism, this neuropeptide may be of major importance in cerebrovascular regulation.