Cytokines such as interleukin-1 (IL-1) are thought to contribute to the inflammatory response associated with autoimmune diseases like multiple sclerosis. We assessed the role of IL-1 in an animal model of MS, experimental allergic encephalomyelitis (EAE), by testing the effects of treatment with an IL-1 receptor antagonist (recombinant human IL-1ra) on the clinical course of EAE in Lewis rats. Treatment with rhIL-1ra every day starting on Day 9 post-immunization with myelin basic protein (MBP) during the effector phase of EAE significantly inhibited clinical signs of EAE. rhIL-1ra delayed the onset, reduced the severity of paralysis and weight loss, and shortened the duration of disease. These data suggest that IL-1 is a mediator of the inflammation resulting from active immunization with MBP, and that inhibitors of IL-1 may prove beneficial for the treatment of autoimmune or inflammatory diseases of the central nervous system.