Administration of the γ-aminobutyric acid (GABA) receptor agonist, muscimol, into the third ventricle of anesthetized cats causes decreases in blood pressure and heart rate. To determine the brain areas involved, we administered muscimol into the (1) entire ventricular system, (2) lateral and 3rd ventricles, and (3) 4th ventricle. Muscimol 0.05-16.65 μg administered into the entire ventricular system resulted in dose-dependent decreases in blood pressure, and at the two highest doses of 6.65 and 16.65μg, significant reductions in heart rate. These changes in blood pressure and heart rate were mimicked when muscimol was localized to the 4th ventricle. Pressure and rate changes were not observed when muscimol was restricted to the lateral and 3rd ventricles. To determine the autonomic nerves involved in mediating the responses produced by muscimol administered into the 4th ventricle, bilateral vagotomy and bilateral stellate ganglionectomy were performed. Vagotomy had no effect on the responses evoked by muscimol, whereas stellate ganglionectomy prevented the decrease in heart rate without altering the effect of muscimol on blood pressure. To determine the efficacy of muscimol, the hypotensive and bradycardic effects of this agent were compared to those obtained with clonidine. The depressor response obtained with muscimol was greater than that seen with clonidine. In addition, muscimol produced an additional fall in pressure after a plateau effect had been obtained with clonidine; the converse was not observed. Pretreatment with the GABA receptor antagonist, bicuculline (25-100μg) administered into the fourth ventricle in doses which had no effects on blood pressure or heart rate prevented the effect of muscimol. Treatment with bicuculline after a peak response had been obtained with muscimol restored pressure and rate to normal. These results indicate that activation of GABA receptors in the region of the hindbrain causes hypotension and bradycardia, and that both of these responses are mediated by a reduction in sympathetic outflow to the vasculature and heart.Circ Res 47: 80-88, 1980