HLA-DR-immunoreactive microglia were quantitated in the middle temporal gyrus of five late-stage patients with Alzheimer's disease (AD) and five age-matched control subjects using LN3 immunocytochemistry and computerized morphometric image analysis. The grand mean numerical density of HLA-DR-immunoreactive microglia in AD (403.86/mm2) was significantly larger than in the five control subjects (193.33/mm2) (p < 0.0001). The grand mean cross-sectional area of HLA-DR-immunoreactive microgiia in AD subjects (222.90 μm2) was significantly larger than in control subjects (121.59 μm2) (p < 0.0001). The percentage of total microglia that were large activated microglia was much greater in AD (47.9%) than in control subjects (15.2%). The grand mean percent of the cortical area occupied by HLA-DR-immunoreactive microglia in AD (9.02%) was significantly greater than in controls (2.35%) (p < 0.0001). Microglia were present in greater numbers in the outer three cortical laminae in both AD and controls. The striking increase in activated microglia in the neocortex and their role in the inflammatory response and possible secretion of neurotoxins could be important in neuron degeneration in AD.