We evaluated in vivo the effect of aging on the sigma(1) receptors in the monkey brain by the quantitative analysis of the binding of [11C]SA4503 to sigma(1) receptors with positron emission tomography. Based on a three-compartment model, the influx rate constant K(1) of [11C]SA4503 from plasma to brain across the blood-brain barrier in all 10 regions investigated became smaller in the aged monkeys (20-28 years old, n=5) than in the young adult monkeys (4-8 years old, n=5), but the reduction was not significant due to the individual differences. On the other hand, the binding potential, which was calculated as the ratio of the association rate constant k(3) to the dissociation rate constant k(4) for the binding of [11C]SA4503 to sigma(1) receptors in the brain, significantly increased in nine of the brain regions of the aged monkeys to the 160-210% levels of the young monkeys. We concluded that the sigma(1) receptor binding sites increased in the aging process of the monkey brain.