To investigate the possible role of brain endothelin-1 (ET-1) in hypertension of spontaneously hypertensive rats (SHRs), we measured immunoreactive (ir) ET-1 contents in brain regions as well as plasma ir-ET-1 levels in SHRs aged 4-5 and 12-14 weeks and age-matched Wistar-Kyoto rats (WKY) with a radioimmunoassay for ET-1. Systolic blood pressures of SHR aged 4-5 and 12-14 weeks were significantly higher than those of corresponding WKY. Significant amounts of ir-ET-1 were detectable throughout the discrete brain regions analyzed in both strains; higher ir-ET-1 contents in structures such as thalamus, hypothalamus, midbrain, pons, medulla, and cerebellum, with the lowest in cerebral cortex, were observed. A reverse-phase high-performance liquid chromatography of the brain extracts revealed the presence of both a major component identical to the elution position of synthetic ET-1 and a minor component possibly corresponding to its oxidized form. When compared, ir-ET-1 contents in all brain regions analyzed were lower in SHRs than in WKY rats. This strain-related change of ir-ET-1 contents was significant in the medulla at 4-5 weeks of age, and in all brain regions except hypothalamus at 12-14 weeks of age. Plasma ir-ET-1 levels, in contrast, were comparable between SHRs and WKY rats. These results suggest that brain ET-1 may be involved in the development and the maintenance of hypertension in SHRs.