We tested the hypothesis that sympathetic nerves influence cardiocyte organelle volumes and capillarity in spontaneously hypertensive rats (SHR) with long-standing hypertension and left ventricular hypertrophy. SHR and their normotensive, Wistar Kyoto (WKY), controls were treated with 6-hydroxydopamine from birth to prevent the establishment of the sympathetic nervous system. To determine whether beta adrenergic receptors were the major pathway of sympathetic influence, another group of SHR and WKY were chronically treated from weaning with the beta 1 adrenergic antagonist, metoprolol. In SHR sympathectomy failed to alter, while metoprolol attenuated, hypertension. Stereological analyses of perfuse-fixed hearts showed that in both SHR and WKY mitochondria/myofibrils volume ratio was increased by long-term sympathectomy, mainly by limiting mitochondrial volume density, even though this intervention failed to alter left ventricular mass. In contrast, long-term beta 1 blockade attenuated hypertrophy in SHR but had no effect on mitochondria/myofibrils volume ratio. Capillary numerical density was increased significantly in sympathectomized SHR and WKY. However, despite this increase, capillary volume density was similar in control and sympathectomized rats, since capillary diameter was less in the latter. Metoprolol-treated SHR showed a trend toward higher capillary numerical densities consistent with their attenuation of hypertrophy. These findings indicate that sympathetic nerves, either directly or indirectly, inhibit cardiocyte mitochondrial growth and capillary proliferation during both normal and pressure-overload induced cardiac enlargement.