This study was undertaken to determine if central nervous system differences in blood pressure regulation exist between spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) controls. Central control mechanisms were examined by observing the effects of posterior hypothalamic (PH) stimulation upon preganglionic sympathetic activity in 14--18 week old SHR and WKY rats. A bipolar, concentric electrode was stereotaxically placed in the PH. Stimulation was delivered at 20, 60 and 100 Hz (3-sec duration, 0.1 msec pulse width) at a voltage twice that producing an increase in blood pressure (less than 5 mm Hg) at 60 Hz. Sympathetic activity was recorded from a portion of the splanchnic nerve just distal to the diaphragm. Blood pressure was measured from a femoral artery catheter. SHR responded with greater increases in sympathetic activity than WKY; the differences were statistically significant at 60 and 100 Hz. SHR also responded with significantly greater increases in blood pressure at all frequencies of stimulation. To determine if the enhanced sympathetic response to PH stimulation seen in adult SHR is an intrinsic difference rather than secondary to sustained hypertension, we maintained SHR normotensive from four weeks of age with antihypertensive drug therapy (clonidine or hydralazine). Chronically treated animals were then tested at 14--18 weeks of age while on antihypertensives or four days after drug discontinuance. Sympathetic and blood pressure responses to PH stimulation were significantly greater in SHR maintained normotensive than untreated or chronically treated WKY. These data support the concept that a central factor is involved in the etiology of hypertension in the SHR.