Previous investigations indicate that the spontaneously hypertensive rat (SHR) has elevated sympathetic tone at rest. The present study aimed to determine whether SHR has exaggerated sympatho-adrenal activation in response to various sympathetic stimuli. The mean blood pressure (MBP), heart rate (HR) and preganglionic adrenal sympathetic nerve activity (SNA) were recorded from conscious, unrestrained SHR and from its normotensive control, the Wistar-Kyoto rat (WKY) (n=7, respectively).Ganglionic blockade (trimethaphan, 5 mg/kg) reduced MBP identically in both groups of rats. It did not change HR in SHR, but increased HR significantly in WKY (P<0.05). The adrenal SNA increased in both groups, but the magnitude of the increase was more than threefold greater in SHR (P<0.05). Mental stress caused by air-jet induced significantly greater tachycardia (threefold) and sympatho-adrenal activation (tenfold) in SHR than in WKY rats. In SHR the inhibition of glycolysis (2-deoxy-d-glucose, 500 mg/kg) also produced a profound activation of adrenal SNA (sevenfold) and the increased adrenal SNA was not paralleled by an increased HR. We conclude that a variety of sympathetic stimuli, including ganglionic blockade, mental stress and neuronglucopenia, cause exaggerated activation of preganglionic adrenal SNA in SHR compared with WKY, indicating that adrenal SNA in SHR is hyper-responsive.