Activation of neurons in the region of the dorsomedial hypothalamus (DMH), by microinjection of the GABA(A) receptor antagonist bicuculline methiodide (BMI) results in increases in arterial pressure, heart rate as well as behavioral changes similar to those evoked by acute emotional stress. Previous anatomic studies clearly demonstrated projections from the DMH to the midbrain periaqueductal gray (PAG), a brain region implicated in the organization of behavioral strategies associated with specific cardiovascular responses. In this study, physiological experiments in conscious rats were used to investigate the functional significance of this pathway. Unilateral inhibition of the lateral dorsolateral region of the PAG (l/dlPAG) with the GABA(A) receptor agonist, muscimol (1 nmol/100 nl) largely reduced the tachycardia and the pressor response produced by microinjection of BMI (10 pmol/100 nl) into the ipsilateral DMH. In contrast, inhibition of the ventrolateral PAG (vlPAG) region had no significant effect on the cardiovascular response evoked from disinhibition of the ipsilateral DMH. Our present results indicate that the l/dlPAG region is an important synaptic relay in the descending cardiovascular pathways from the DMH.