Food restriction increases the maximal longevity of rats. Male rats do not increase their food intake to compensate for the increase in energy expenditure in response to exercise. However, a decrease in the availability of energy for growth and cell proliferation that induces an increase in maximal longevity in sedentary rats only results in an improvement in average survival, with no extension of maximal life span, when caused by exercise. In a previous study (J.O. Holloszy and K.B. Schechtman. J. Appl. Physiol. 70:1529-1535, 1991), to test the possibility that exercise prevents the extension of life span by food restriction, wheel running and food restriction were combined. The food-restricted runners showed the same increase in maximal life span as food-restricted sedentary rats but had an increased mortality rate during the first one-half of their mortality curve. The purpose of the present study was to determine the pathological cause of this increased early mortality. However, in contrast to our previous results, the food-restricted wheel-running rats in this study showed no increase in early mortality, and their survival curves were virtually identical to those of sedentary animals that were food restricted so as to keep their body weights the same as those of the runners. Thus it is possible that the rats in the previous study had a health problem that had no effect on longevity except when both food restriction and exercise were superimposed on it. Possibly of interest in this regard, the rats in this study did considerably more voluntary running than those in the previous study. It is concluded that 1) moderate caloric restriction combined with exercise does not normally increase the early mortality rate in male rats, 2) exercise does not interfere with the extension of maximal life span by food restriction, and 3) the beneficial effects of food restriction and exercise on survival are not additive or synergistic.