The SA gene was initially identified by differential hybridisation because of its higher expression in the kidney of the spontaneously hypertensive rat (SHR) compared with the normotensive Wistar-Kyoto rat. In subsequent studies, the allele of the SA gene from the SHR and several other genetically hypertensive strains was found to cosegregate with increased blood pressure in F2 progeny derived from crosses with normotensive rats. The increased expression of the SA gene in the kidney of the SHR occurs early, before the rapid rise in blood pressure in this model, is genotype-dependent and localised to the proximal tubule. Although the functions of its protein product remain to be elucidated, these findings raise the exciting possibilities that: (i) SA represents a major component of an important novel system regulating blood pressure, and (ii) it underlies a primary renal mechanism predisposing to hypertension.