Using a model of perinatal brain lesions induced by lipopolysaccharide and hypoxia/ischemia, we hypothesized that interleukin-2 (IL-2), a neurotoxic cytokine, was enhanced within injured brains. We showed that lipopolysaccharide and hypoxia/ischemia enhanced both intracerebral IL-2 mRNA and protein levels, with a maximum increase upon lipopolysaccharide and hypoxia/ischemia. The lack of detectable T lymphocytes suggested the synthesis of IL-2 by neural cells. Lipopolysaccharide and hypoxia triggered IL-2 synthesis by cultured microglia with a peak after exposure to lipopolysaccharide and hypoxia. Double-labeling showed, in vivo and in vitro, that IL-2 immunoreactivity was colocalized with a microglia/macrophage marker. These results disclosed the ability of microglia to produce IL-2 and also suggest the implication of IL-2 in neural cell death triggered by perinatal lipopolysaccharide and hypoxia/ischemia exposures.