Galanin-like peptide (GALP) is a neuropeptide that has complex actions on energy balance, producing orexigenic effects in the short term in rats but anorexigenic and febrile effects over the longer term in rats and mice. GALP is thought to promote feeding via neuropeptide Y and orexin neurons, but the mediators of the anorexia are unknown. However, the anorexic and febrile actions of GALP are similar in magnitude and profile to those seen after central injections of the cytokine IL-1. Thus, the aim of this study was to test the hypothesis that IL-1 mediates the effects of GALP on energy balance. Intracerebroventricular injection of GALP (1.5 nmol) in male Sprague-Dawley rats stimulated production of IL-1alpha and IL-1beta protein in macrophages and/or microglia in selected brain areas, including the meninges, and periventricular brain regions. Intracerebroventricular injection of GALP in rats stimulated food intake over 1 h but decreased feeding and body weight at 24 h and caused a rise in core body temperature over 8 h. Coinfusion of the IL-1 receptor antagonist had no effect on the GALP-induced orexigenic response but significantly reduced the longer-term actions of GALP observed at 24 h and its effect on body temperature. Furthermore, the actions of GALP on feeding, body weight, and body temperature were significantly reduced in IL-1alpha/beta-, IL-1beta-, or IL-1 type I receptor (IL-1RI)-deficient mice. These data suggest that GALP induces expression of IL-1 in the brain, and its anorexic and febrile actions are mediated by this cytokine acting via IL-1 type I receptor.