Male rats that exercise in running wheels have a longer average survival than freely eating sedentary controls but, in contrast to food-restricted sedentary controls of the same weight, show no extension of maximal life span (J. Appl. Physiol. 59: 826-831, 1985). To test the possibility that exercise may counteract a life-extending effect of decreased availability of energy for certain biological processes such as cell proliferation, we examined the combined effects of exercise and food restriction on longevity of male rats. As before, wheel running improved average length of life, 978 +/- 172 vs. 875 +/- 175 (SD) days, for the sedentary controls (P less than 0.01) without increasing maximal life span. Paired-weight controls, food restricted (approximately 30% below ad libitum) to weight the same as the runners, showed increases in both average (1,056 +/- 144 days) and maximal life span. Food-restricted runners, with intake restricted to the same extent (approximately 30%), had an increased mortality rate over the first approximately 50% of their survival curve up to approximately 900 days of age; their average life span (995 +/- 226) was similar to that of the control group of runners and shorter than that of their paired-weight food-restricted sedentary controls (1,088 +/- 159 days, P less than 0.05). However, after approximately 900 days of age the food-restricted runners' survival became similar to that of the food-restricted sedentary groups, with a comparable increase in maximal life span. Thus the exercise did not counteract the increase in maximal life span induced by food restriction.(ABSTRACT TRUNCATED AT 250 WORDS)