Oxidative stress is a basic mechanism involved in both age and smoking-related diseases. To test whether smoking affects young, old, and calorie-restricted organisms to the same extent, we assessed oxidative stress parameters in the lung, heart, and liver of male Fischer 344 rats (4 months old and 19–22 months old) exposed to air or cigarette mainstream smoke. Smoke-related effects were seen for parameters of DNA damage, lipid peroxidation, protein oxidation, and glycoxidation. No smoke-related effects were observed for DNA damage in the lung and heart (Comet assay) and for malondialdehyde in the lung. The old rats showed higher smoke-related responses than the young rats for 8-hydroxy-desoxyguanosine (8-OHdG) in the heart and liver, DNA damage in the liver, and protein carbonyls in the lung; however, there was little evidence for an overadditive effect of smoking on aging. Caloric restriction, which is known to retard aging effects, also had little impact on smoke-related oxidative changes.