The involvement of endogenous growth-hormone-releasing hormone (GHRH) in the sleep-promoting activity of interleukin-1 (IL1) was studied. The effects on sleep of intracerebroventricular injection of IL1 were tested in rats pretreated with intracerebroventricular antibodies to GHRH (GHRH-ab). One group of rats received two treatments each consisting of two injections, control IgG + physiological saline (IgG + Sal) and on another day GHRH-ab + Sal, whereas another group of rats received IgG + Sal, IgG + IL1 and GHRH-ab + IL1 on separate days with one day off between the various treatments. IgG or GHRH-ab was injected 6 h prior to dark onset; Sal or IL1 was administered at dark onset. Recording of sleep-wake activity and cortical brain temperature (Tcrt) was started with the injection of IgG or GHRH-ab and continued for 18 h. GHRH-ab (GHRH-ab + Sal) suppressed rapid eye movement sleep (REMS), non-REMS (NREMS) and EEG slow-wave activity (SWA) during NREMS throughout the recording period. IL1 treatment (IgG + IL1) enhanced NREMS and SWA, and induced fever for 6 h. Pretreatment with GHRH-ab (GHRH-ab + IL1) abolished the IL1-induced increases in NREMS, attenuated the enhancements in SWA, and suppressed fever for 6 hours after IL1. The results indicate that the sleep-promoting activity of IL1 is mediated at least in part via GHRH. The suppression of the IL1-induced fever by GHRH-ab might be attributed to an inhibition of hypothalamic somatostatin.