The goals of this study were to examine the effects of three months of voluntary wheel-running exercise on life span, whole body and brain, heart and adrenal weights and biogenic amine content (norepinephrine, dopamine, epinephrine and serotonin) in three age groups of male mice. The three groups consisted of mature (9 months), middle-aged (19 months), and old (27-29 months) mice. No significant differences in weight were found between control and exercise or age. The oldest mice had a survival rate of 69% for the exercise group and 43% for the age matched controls when the exercise phase was completed. Locomotor activity was significantly reduced for the old mice compared to the middle-age and mature mice. Only the mature (12 months of age at sacrifice) exercised mice showed a cardiac and adrenal hypertrophy (about 10%). There was a moderate increase in norepinephrine content in the ventral hypothalamus of the brain with exercise (significant at 12 months of age). Biogenic amine content in other regions of the brain (brain stem and forebrain minus hypothalamus) was not affected by age and/or exercise. There was a significant decrease in heart norepinephrine content with exercise in old mice (30-32 months). Adrenal gland norepinephrine content was significantly increased by exercise at 12 months of age and decreased at 22 months of age. Our results suggest that an increase in norepinephrine content in the hypothalamus might be a manifestation of an adaptation to the increased demands upon hypothalamic noradrenergic terminals imposed by prolonged exercise. It is also apparent that aging and exercise alters the amounts of sympathetic transmitter of the heart and adrenal glands. Such alteration may be beneficial to the aging brain by retaining norepinephrine stores that normally decline with age.