The central administration of immune cytokines such as interleukin-1 (IL-1) and interferon-alpha (IFN-alpha) results in the suppression of peripheral cellular immunity, which depends, at least partly, on the sympathetic nervous activity. An intrathird cerebroventricular (I3V) infusion of recombinant human IL-1 beta (rhIL-1 beta) (1-5 ng/rat) elicited a dose-dependent increase in the electrical activity of the splenic sympathetic nerve in urethane and alpha-chloralose anesthetized rats. The effect of rhIL-1 beta (1 ng/rat) was completely blocked by pretreatment with an IL-1 receptor antagonist (1 microgram/rat, I3V 10 min before rhIL-1 beta), sodium salicylate (1 microgram/rat), or alpha-melanocyte stimulating hormone (alpha-MSH) (400 ng/rat). Furthermore, an antagonist of corticotropin-releasing factor (CRF), alpha-helical CRF9-41 (2 micrograms/rat), completely abolished the rhIL-1 beta-induced increase in the splenic nerve activity, although an I3V infusion of CRF (1 microgram/rat) excited it. These results suggest that IL-1 beta in the brain activates splenic sympathetic activity by its receptor-mediated and prostaglandin-dependent action that is sensitive to alpha-MSH, depending on CRF system. Our findings, together with the previous results, suggest that the splenic sympathetic nerve represents one of the communication channels from the brain to the immune system.