Abstract: Neuronal pathways involved in stress responses to extreme somatosensory stimuli were investigated by immunostaining, viral tract tracing, and experimental brain surgery in rats. Acute audiogenic stress, which elicits an immediate marked elevation in plasma ACTH and corticosterone concentrations, was used as a model. Loud noise (105 dB, 30 min) elicited c-fos activation within neurons in all of the components of the auditory system and stress-sensitive brain nuclei, including corticotropin-releasing hormone-synthesizing parvicellular neurons in the hypothalamic paraventricular nucleus (PVN). c-Fos activation was also seen in the medial paralemniscal nucleus in the pons (MPL) and in the subparafascicular nucleus (SPF) in the midbrain. After injection of neurotropic virus (pseudorabies, Bartha strain) into the PVN, neurons in the MPL and the parvicellular portion of the SPF were retrogradely infected. It has been shown by immunostaining that MPL and SPF neurons express a newly discovered neuropeptide, tuberoinfundibular peptide of 39 residues (TIP39). TIP39 is present in a fine neuronal network in the PVN. Audiogenic stress-elicited c-fos activation in TIP39-containing neurons of the MPL and SPF. TIP39 immunoreactivity disappeared from the PVN after transection of MPL and SPF projections to the nucleus. These observations suggest that TIP39-containing MPL and SPF neurons may participate in mediating audiogenic stress responses.