The present study was undertaken to investigate the influence of ethanol on the cardiac antioxidant defense system of mice exposed to cigarette smoke. Cigarette smoke exposure for 10 wk led to an increase in the levels of lipid peroxidation in the heart. These levels increased further in animals co-exposed to ethanol and cigarette smoke. Concomitantly, the levels of glutathione were found to decrease after cigarette smoke exposure. In the animals co-exposed to ethanol and cigarette smoke, there was a further decrease in glutathione levels. Catalase activity increased in the animals exposed to cigarette smoke; this activity increased further with combined exposure to cigarette smoke and ethanol. On the other hand, superoxide dismutase (SOD) activity was not affected by cigarette smoke exposure, while it increased in the ethanol-exposed group. SOD activity was higher in the hearts of animals co-exposed to cigarette smoke and ethanol as compared to animals that received ethanol alone. The activity of heat-stable lactate dehydrogenase in serum was not affected when the animals were exposed to either cigarette smoke or ethanol, whereas this activity was observed to be elevated in animals co-exposed to cigarette smoke and ethanol. It appears from these results that ethanol potentates the cigarette-smoke-induced peroxidative damage to heart.