Interleukin-1 (IL-1) is known to regulate gastric functions via a central action at the hypothalamic level, and it has also been shown that this cytokine can directly modulate rat gastric motility. This study was conducted to determine whether IL-1 beta is produced and released by rat gastric fundi in vitro. IL-1 beta immunoreactivity was released in measurable amounts from explanted rat gastric tissue. This release was not affected by electrical stimulation of the gastric strips or by agents that induce IL-1 biosynthesis. It could be inhibited only by the glucocorticoid dexamethasone. Ex vivo experiments confirmed the inhibitory role of glucocorticoids and showed that IL-1 beta release can be inhibited by agents that reduce gastric acid secretion, suggesting that the latter might stimulate IL-1 beta synthesis and release. In light of the well-established gastroprotection exerted by IL-1, H(+)-induced IL-1 beta release might serve as a protection against mucosal injuries caused by acid secretion, and the inhibition of this release by glucocorticoids might be involved in the pathogenesis of gastric damage associated with severe stress or steroid therapy.