Dietary restriction (DR) slows the rate of aging in laboratory rodents but the mechanism of action is unknown. DR is known to induce beneficial effects in a variety of tissues and organ systems. DR also maintains high levels of physical activity over the life span. We tested the hypothesis that lifelong physical activity is an important component of the anti-aging action of DR. Male specific pathogen-free Fischer 344 rats were divided into 4 groups at 6 weeks of age: A: fed old libitum; AE: fed ad libitum and in cages with running wheels; B: fed 60% ad libitum; BE: fed 60% ad libitum and in cages with running wheels. Running activity and spontaneous cage activity were measured over 24 hours and over the life span. Metabolic rate was measured indirectly by analysis of air entering and leaving cages. AE rats exhibited low levels of running activity and ran very little beyond 6 months of age. In contrast, BE rats sustained high running levels even after all A and AE rats had died. High levels of wheel running did not decrease spontaneous cage activity. Median life span (50% survival) was in the order A = AE < B < BE. Ten percent survival was in the order A = AE < B = BE. BE rats had greatest median life span and also highest specific metabolic rate. Exercise and DR altered pathology: At death BE rats had a high incidence of cardiomyopathy, whereas A and AE rats had high incidence of chronic nephropathy and pituitary tumors. The data indicate that increased physical activity is probably not an important factor in the action of DR on aging.