Two distinct species of amyloid beta protein (A beta) with different carboxyl termini, A beta 40 and A beta 42(43), are deposited in plaques in the brains of patients with Alzheimer's disease and Down's syndrome. The relationship between these two forms of A beta and microglial cells was investigated in 16 subjects with Down's syndrome ranging in age from 31 to 64 years. The amount of A beta 40 in plaques was low in persons under 50 years of age, even though high amounts of A beta 42(43) were present. Microglia were observed most commonly in plaques containing both A beta 40 and A beta 42(43) but less commonly in those with A beta 42(43) alone. The presence of microglial cells in plaques may be associated with the accumulation of A beta 40 and these cells may have a role in the production or processing of this particular molecular species.