Brain corticotropin-releasing factor (CRF) is involved in stress-related alterations of gastric acid secretion. CRF in the locus coeruleus has been shown to induce anxiogenic behavioral responses and to mimic stress-induced alterations of colonic motor function. Whether the locus coeruleus/subcoeruleus nucleus (LC/SC) is a site of action for CRF to alter gastric acid secretion was investigated in urethane-anesthetized gastric fistula rats. In sham-operated animals, CRF (126-420 pmol) microinfused bilaterally into the LC/SC induced a dose-dependent inhibition of pentagastrin (PG)-stimulated gastric acid secretion of 60-81% within the first hour after microinjection. At the 420 pmol dose, this inhibitory effect of CRF into the LC/SC lasted throughout the whole observation period of 120 min. After bilateral vagotomy, basal and PG-stimulated gastric acid secretion at microinjection of vehicle was reduced. Nevertheless, microinfusion of 420 pmol CRF into the LC/SC still inhibited significantly gastric acid secretion by 62.1%. In contrast, in spinal cord transected animals bilateral microinfusion of 420 pmol CRF into the LC/SC did not reduce PG-stimulated gastric acid secretion. These data indicate that CRF acts in the LC/SC to induce a long lasting inhibition of peripherally stimulated gastric acid secretion via spinal pathways. These findings suggest a possible role of the LC/SC in the regulation of gastric secretion and of endogenous CRF at these sites in the stress-related inhibition of gastric acid secretion by affecting autonomic nervous system activity.