In this study, we have investigated the release of immunoreactive interleukin-1 beta (irIL-1 beta) from the rat hypothalamus in vitro. It was found that (1) tissue explants release sizable amounts of irIL-1 beta (ranging from 0.43 to 0.52 pg/mg of wet tissue) in 20 min incubations; (2) basal release in significantly increased by depolarization induced with 56 mM KCl; (3) K(+)-induced irIL-1 beta release is inhibited by the specific blocker of N-type calcium channels, omega-conotoxin, and by verapamil, but not by nifedipine; (4) K(+)-induced release is also inhibited by the Na+ channel blockers tetrodotoxin and lidocaine; (5) irIL-1 beta release is significantly increased by noradrenalin; such increase is antagonized by verapamil and the beta-blocker propranolol, but not by the alpha-blocker phentolamine. The present evidence suggests that irIL-1 beta released by rat hypothalamic explants following KCl depolarization is neuronal in origin.