Previous studies in our laboratory have indicated free radical participation in magnesium deficiency cardiomyopathy. In this study, we examined the capacity of the magnesium-deficient animals to withstand an in vivo oxidative stress. Syrian hamsters were placed on either magnesium-deficient diet or a magnesium-supplemented control diet. Animals from each group also received vitamin E. After 14 days some of animals were given the catecholamine isoprenaline; 2 days later the animals were killed. The severity of the isoprenaline-induced injury was assessed by a morphometric analysis. The isoprenaline-induced injury was dramatically increased in the magnesium-deficient animals. The addition of vitamin E reduced the severity of the injury by 81% in these animals, indicating that the injury process was primarily due to an oxidative mechanism. These data show that magnesium deficiency increases the susceptibility of the cardiovascular system to oxidative stress.