The effects of stimulation in the paraventricular nucleus (PVN) of the hypothalamus on the development of gastrointestinal ulceration have been examined in urethan-anesthetized male Sprague-Dawley rats. Electrical stimulation (200 microA, 60 Hz, 100-microseconds pulse width) in the PVN was performed for 1 h, after which samples of the stomach and duodenum were fixed for subsequent histological assessment of damage. Such damage was scored, blindly, on a 0 (normal) to 3 (severe) scale. Stimulation in the PVN resulted in necrosis and hemorrhage in both the stomach (mean damage score of 1.8 +/- 0.3) and duodenum (1.7 +/- 0.4). In contrast, similar stimulation in regions immediately adjacent to the PVN was found to be without significant effect on the stomach (0.3 +/- 0.1) or duodenum (0.6 +/- 0.2). In a second series of studies PVN stimulation following bilateral vagotomy resulted in damage scores (stomach: 0.2 +/- 0.1; duodenum: 0.1 +/- 0.1) that were significantly reduced compared with the PVN-stimulated vagal-intact group (P less than 0.05) but were not significantly different from the group stimulated in regions outside the PVN (P greater than 0.1). These data suggest an important role for PVN efferents influencing medullary vagal preganglionic neurons in the development of acute gastroduodenal ulceration.