Interleukin-1 alpha-immunoreactive (IL-1 alpha+) microglia are prominent components of neuritic plaques in Alzheimer's disease, and may be important in the evolution of neuritic plaques from diffuse amyloid deposits. Neuritic plaques show a characteristic distribution across cerebral regions and are absent in the cerebellum of patients with Alzheimer's disease. We used single- and dual-immunohistochemical labelling to investigate the possibility that the expression of IL-1 alpha is correlated with this regional distribution of neuritic (tau 2-immunoreactive, tau 2+) plaques. In Alzheimer's disease, tau 2+ neuritic plaques occurred with increasing frequency in grey matter of frontal and occipital lobes, temporal lobe, and hippocampus. There were positive correlations between the regional patterns of distribution of activated IL-1 alpha+ microglia and tau 2+ neuritic plaques as well as between activated IL-1 alpha+ microglia and activated astrocytes. No activated IL-1 alpha+ microglia, tau 2+ neuritic plaques, or activated astrocytes were observed in cerebellum of these Alzheimer patients. These regional relationships between activated IL-1 alpha+ microglia, tau 2+ neuritic plaques, and activated astrocytes, together with the established functions of IL-1, support a causal association between the overexpression of IL-1 and the evolution of beta-amyloid deposits into neuritic plaques in Alzheimer's disease.