A series of measurements was made to assess the morphology of the brain of the spontaneously hypertensive rat (SHR). The SHR brain was smaller than that of age-matched normotensive Wistar-Kyoto (WKY) controls in a majority of measures of external surface landmarks. This reduction in size was evident in the youngest age group examined (94 days) and persisted in older groups (170, 240 and 350 days). The brain of the SHR was also smaller in terms of brain weight and brain weight:body weight ratios. Section-by-section digitized analyses of coronal histologic sections from 94-day-old rats revealed significant reductions in mean cross-sectional area and volume of midbrain/pons (10%) and hindbrain (11%) regions, but not of forebrain, in the SHR. Alterations in the mediolateral dimension, particularly within the pontomedullary brainstem, accounted for more of these volumetric changes than those in the dorsoventral dimension. Using the same coronal sections, it was found that surface areas and volumes of five individual nuclei/fiber tracts, selected for their involvement in central cardiovascular regulation, were significantly decreased in the SHR. The largest reduction in volume (30%) was found in the nucleus tractus solitarius, the primary site of termination of afferent baroreceptor fibers. No differences in surface area or volume were found in that portion of the cerebroventricular system (aqueduct of Sylvius) associated with the periventricular grey region, or in the inferior colliculus, which is not thought to be involved in cardiovascular control. These observations not only have practical implications, but suggest that the pathophysiological condition expressed as spontaneous hypertension in this widely-used model may be related to morphological alterations in the central nervous system.