To assess whether amyloid plaque accumulation in the monkey brain can account for age-related cognitive impairment that begins at about 20 years of age, we measured plaque content in the brains of 14 rhesus monkeys aged 5-30 years. We used immunohistochemistry employing the monoclonal antibody 6E10, which is specific to amino acids 1-17 of the amyloid beta peptide to identify amyloid plaques in serial coronal sections of the forebrain. Amyloid plaques accumulate with age, starting at 25 years of age and escalating after 30 years. Until the age of 30, plaques are only found in a few monkeys and are relatively sparse. Results from our group and others show that plaque content and the proportion of individuals afflicted with amyloid plaques increase with age. Although both cognitive dysfunction and plaque content increase with age, amyloid plaque content does not correlate with the cognitive dysfunction observed in elderly monkeys since even in very old subjects some cognitively impaired animals have few amyloid plaques and others with abundant plaques show only minor cognitive impairments. In summary, amyloid plaques appear to accumulate significantly only in monkeys over 25 years of age but do not appear to be a causal factor in age-related cognitive decline of the normal aging rhesus monkey.