Neuropeptide Y (NPY), one of the most abundant neuropeptides found in the central nervous system (CNS), has been implicated in the regulation of many autonomic functions, including cardiovascular control and the central stress response. The present study represents a detailed investigation of the effects of acute and chronic restraint stress on the expression of the mRNA encoding the NPY precursor, prepro-NPY, in the CNS of normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) using in situ hybridization histochemistry. Basal (unstressed) levels of prepro-NPY mRNA expression were found to be significantly increased in the hypothalamic arcuate nucleus of SHR compared to WKY rats, with similar levels of prepro-NPY mRNA expression found in the remaining central nuclei. Following exposure to both acute and chronic restraint, significant changes in prepro-NPY mRNA expression were found in a variety of central regions in both strains, including the arcuate nucleus and hippocampus (both strains), medial amygdala and cortex (WKY only), and dentate gyrus, nucleus of the solitary tract and ventrolateral medulla (SHR only). A comparison of the temporal response to restraint revealed that significant differences between strains existed in regions such as the arcuate nucleus, hippocampus and dentate gyrus, providing further evidence that hypertensive rats apparently have an impaired neural stress response. The present study demonstrates that exposure to restraint results in significant changes in prepro-NPY mRNA expression in specific nuclei of both WKY and SHR that are components of not only the central circuitry regulating the stress response, but also the neural network modulating autonomic function.