Audiogenic stress is known to activate the hypothalamo-pituitary-adrenocortical (HPA) axis in rats. The goal of the present study was to determine whether the medial geniculate nuclei (including all auditory nuclei of the thalamus), which are obligatory relays in the transmission of auditory information to the forebrain, are critically involved in HPA activation by audiogenic stress. To this end, corticosterone levels and regional brain activity indexed by c-fos mRNA induction, elicited by 30 min of 105 dB white noise, were measured. Compared with unoperated and sham-operated rats, complete medial geniculate nuclei lesions blocked corticosterone release normally induced by loud noise. The effects of the lesions were specific to loud noise insofar as corticosterone release in response to restraint or ether stress was not reduced in lesioned rats. We have determined previously that audiogenic stress is associated with a specific regional pattern of c-fos mRNA induction. Rats sustaining complete medial geniculate lesions demonstrated a blockade of c-fos mRNA induction in several audiogenic stress responsive regions, also known to directly innervate medial parvocellular neurons of the paraventricular hypothalamic nucleus. Thus, in addition to blockade in the paraventricular hypothalamic nucleus, c-fos mRNA induction in the lesioned animals was abolished in the bed nucleus of the stria terminalis, especially its anterior medial and ventral aspects, the septohypothalamic nucleus, and the anteroventral preoptic area, compared with unoperated and sham-operated rats. Several additional regions in the lesioned rats failed to show reliable c-fos mRNA induction compared with naive rat controls. Nearly all other regions that showed reliable c-fos mRNA induction in the unoperated and sham-operated rats displayed either similar or slightly reduced levels in complete medial geniculate-lesioned rats, suggesting that these regions are not part of a critical HPA activational circuit in response to audiogenic stress. On the basis of these results, putative circuits from the medial geniculate nuclei to the paraventricular nucleus of the hypothalamus involved in activation of the HPA axis by audiogenic stress are discussed.