The paraventricular nucleus (PVN) contains neurons that release corticotrophin-releasing factor (CRH) and thus provide the stimulus for the release of adrenocorticotrophic hormone (ACTH), the neuroendocrine hallmark of the response to stress. However, inhibition of neuronal activity in the nearby dorsomedial hypothalamic nucleus (DMH) by microinjection of the GABA(A) receptor agonist muscimol suppresses cardiovascular changes seen in air stress in conscious rats, while similar treatment in the PVN has no effect. Because the DMH projects to the PVN and also contains CRH neurons, we decided to investigate the role of neuronal activity in the DMH in the neuroendocrine response to stress. In control rats or after microinjection of saline vehicle into either the PVN or the DMH, air stress resulted in equivalent increases in plasma levels of ACTH, heart rate, and arterial pressure. Bilateral microinjection of muscimol 80 pmol/100 nl/side into either the PVN or the DMH prior to air stress reduced the associated increases in plasma ACTH (-37% and -71%, respectively), while only injection into the DMH attenuated the accompanying tachycardia (-62%) and pressor (-83%) effects. Thus, neurons in the DMH, but not in the PVN, play a role in both the cardiovascular and neuroendocrine response to air stress.