Marked increases in the brain expression of interleukin (IL)-1 have been reported in rats after permanent occlusion of a large cerebral artery. Interactions between endothelial cells and leukocytes have been implicated in the pathogenesis of several types of ischemic injury to the myocardium and other organs. In this study we asked whether inhibiting the effects of IL-1 would affect the outcome of an experimental brain infarct. Adult male Wistar rats (n = 13) with permanent occlusion of the middle cerebral artery were given IL-1 receptor antagonist. A second group (n = 13) with the same type of brain injury was given a placebo. A third group, subjected to a sham operation, was given either IL-1 receptor antagonist (n = 2) or a placebo (n = 2). Experiments were terminated after either 24 hours or 7 days. Compared with the control group, animals treated with IL-1 receptor antagonist improved their neurological score (P < 0.05), experienced less pronounced changes in body weight (P < 0.05), and had fewer necrotic neurons (P < 0.001) and fewer leukocytes in the ischemic hemisphere (P < 0.001) as well as a smaller area of pallor (P < 0.05) in the ischemis hemisphere. The results suggest that inhibiting the proinflammatory effects of IL-1 with a receptor antagonist is an effective way of influencing the leukocyte responses elicited by an arterial occlusion. Such leukocyte inhibition seemingly attenuates the number of necrotic neurons resulting from the occlusion of a large brain artery.