To determine whether adrenoceptor changes in genetic hypertension occur primary or secondary to blood pressure elevation, we measured cardiac and renal alpha 1- (by [125I]Be 2254 binding) and beta 1- and beta 2-adrenoceptors (by (-)-[125I]iodocyanopindolol binding) densities in various rat models of acquired hypertension (Dahl S rats on a high-sodium diet, 1-clip-1-kidney (1C-1K) renal hypertensive and DOCA-salt hypertensive rats) in comparison with genetically identical age-matched untreated rats. In addition, alpha 1-adrenoceptors were assessed in spontaneously hypertensive rats (SHR) and in SHR treated with the immunosuppressant cyclosporin A. In heart, no clear pattern of changes in alpha 1- or beta 1- and beta 2-adrenoceptors was obtained. In kidney, however, beta 1- and beta 2-adrenoceptors were increased in all models of hypertension, and a good correlation between renal beta-adrenoceptors and systolic blood pressure was found. In contrast, renal alpha 1-adrenoceptors were only increased in SHR but not in any form of acquired hypertension. Thus, renal beta-adrenoceptor increases probably occur secondary to blood pressure elevation, whereas alpha 1-adrenoceptor increases appear to be associated with genetic hypertension. Because renal alpha-adrenoceptors are linked to tubular sodium reabsorption, we suggest that an increase in renal alpha 1- (and alpha 2)-adrenoceptors may be a very early step in the development of genetic hypertension.