In this study, the effect of flight activity on mortality rates and lipoxidative damage in Drosophila was determined to identify mechanisms through which oxidative damage affects life span. The results showed that flies allowed flying throughout life had higher mortality rates and decreased median and maximum life spans compared to controls. The mortality rate of the flight activity group could be lowered, but not completely reversed by switching to control conditions; and the accrued oxidative damage could not be eliminated. The levels of reactive oxygen species produced by mitochondria isolated from high activity and control flies did not differ significantly. However, the high activity flies had altered membrane fatty acid compositions, which made them prone to increased lipid peroxidation. The effect of flight activity on insect life span differs considerably from the beneficial effects of exercise in mammals; these differences may be caused by physiological differences between the two taxa.