The antihypertensive action of central GABA-ergic stimulation was investigated in conscious stroke prone spontaneously hypertensive rats. Injection of the potent GABA agonist musrimol (0.01–1 μg) into the lateral brain ventricle (icv) lowered mean arterial blood pressure (192.1 ± 8.4 mm Hg) dose-dependently in stroke prone spontaneously hypertensive rats with a maximal fall of −52.7 ± 5 mm Hg lasting for about 90 minutes. This was accompanied by bradycardia and sedation. Pretreatrnent with atropine (2 mg/kg, ip, or 15 μg/kg, icv) did not significantly influence the muscimol-induced fall in mean arterial pressure. In normotensive (109.3 ± 1.9 mm Hg) Wistar-Kyoto controls, the maximal decrease in mean arterial pressure was −12.1 ± 1.6 mm Hg from 109.3 ± 1.9 mm Hg, and the duration of the effect was much less than in stroke prone spontaneously hypertensive rats. Following 1 jig muscimol, icv, plasma noradren- aline did not fall significantly in stroke prone spontaneously hypertensive and Wistar-Kyoto rats, but in stroke prone spontaneously hypertensive rats, plasma adrenaline was fully suppressed (from 118.1 ± 24.2 to 22.8 ± 5.7 pg/ml) throughout the depressor response. The efferent sympathetic nervous activity as directly recorded from the n. splanchnicus was similar in conscious stroke prone spontaneously hypertensive and Wistar-Kyoto rats, and was moderately reduced in both strains by 1 μg muscimol, icv. Basal adrenal nerve activity was higher in stroke prone spontaneously hypertensive than in Wistar-Kyoto rats (14.8 ± 3.7 vs. 10.6 ± 1.7 μV, P ± 0.02); it was reduced by 44% in stroke prone spontaneously hypertensive rats and only by 24% in Wistar- Kyoto rats after central muscimol administration. In contrast to muscimol, the central antihypertensive action of the α2-adrenoceptor agonist donidine in conscious stroke prone spontaneously hypertensive rats was accompanied by similar reductions of splanchnic nerve activity (28%) and adrenal activity (25%). Our results demonstrate for the first time an increased efferent adrenal nerve activity in conscious stroke prone spontaneously hypertensive rats and a selective inhibition of the sympathoadrenal pathway by central GABA-ergic stimulation. The antihypertensive action of central GABA receptor stimulation in stroke prone spontaneously hypertensive rats is not mediated by an increase in vagal tone or a generalized reduction in sympathetic tone, but is associated with the selective suppression of sympathoadrenal activity.