Differences in [3H]nitrendipine binding sites in brain regions and subcellular fractions from cortex have been investigated in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. At 4 weeks of age, [3H]nitrendipine receptor binding (Bmax) was increased in the hypothalamus and striatum of SHR but not WKY rats, whereas no changes were found in the cortex, cerebellum, or brain stem. At 12 weeks of age, [3H]nitrendipine binding (Bmax) was still elevated in the hypothalamus of SHR, whereas binding in the striatum was not significantly different. [3H]Nitrendipine binding in SPM-1 membrane from cortex was elevated at 12 weeks of age, whereas no changes were seen in nuclear, mitochondrial microsomal, or SPM-3. These results demonstrate that prior to elevated blood pressure, [3H]nitrendipine receptor binding is increased in discrete brain regions and membrane fractions and suggest that "L" type calcium channels may be under genetic control and be involved in development of hypertension.