The search for factors that influence age-related behavioral and cognitive slowing is ongoing. Because microglia are involved in many neurological disorders, they may also contribute to changes in normal aging. To assess increases in microglial activity, we used an antibody against MHC class II to label microglia in three groups of brains from female Macaca nemestrina: juvenile (2–5 years), young adult (5–11 years), and mature (11–19 years). Image analysis was completed on four white matter and three gray matter regions in a single coronal plane. Microglial expression of MHC class II increased with age, and was highest in the white matter regions of the mature, or middle-aged, monkeys. The higher expression of this antigen may indicate that the cells will more easily respond to stimulation. Their location in the white matter suggest that they may influence myelin loss and the eventual cognitive decline in aged human and nonhuman primates.