Studies were performed to evaluate the possibility that the paraventricular nucleus (PVN) of the hypothalamus modulates gastric acid secretion by changing the sensitivity of the gastric secretory control mechanism to vagal afferent input. Under pentobarbital anesthesia, 17 rats were prepared with esophageal and pyloric catheters such that the stomach could be perfused continuously on a flow-through basis. Thus, acid secretion could be monitored throughout the experiment. Stimulating electrodes were attached to the central cut end of the cervical vagus nerve. Unilateral stimulation of cervical vagal afferents resulted in a substantial increase in gastric acid secretion. This vagal afferent-mediated increase in acid outflow was suppressed following a single PVN lesion ipsilateral to the side of afferent stimulated output. Given the nature of PVN connections with brainstem regions responsible for the elaboration of vago-vagal reflexes, our results suggest that the PVN may control gastric acid outflow by changing the gain of gastric vago-vagal reflexes.