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To identify the site of the increased expression of the SA gene in the kidney of the spontaneously hypertensive rat (SHR) compared with the Wistar-Kyoto (WKY) rat.In situ hybridization of SHR and WKY rat kidney sections with a radioactively labelled rat SA complementary DNA probe.Compared with WKY rat kidney sections, the probe bound intensely to the SHR renal cortex. Binding was sensitive to pretreatment of the section with RNAase A. Microscopic examination after autoradiography showed the increased signal in the SHR to be localized over proximal tubules. Background signal was observed over glomeruli, distal tubules, interlobular arteries and afferent arterioles.The localization of the increased expression of the SA gene in the SHR kidney compared with the WKY rat kidney to the proximal tubule suggests that it might influence blood pressure through effects on tubular function. Several differences in proximal tubular function have already been described between the SHR and WKY rat, and the relationship of these to tubular SA gene expression now need to be investigated. However, in the absence of any known functions for the SA gene product it is also possible that it might act through entirely novel, still undefined mechanisms.