Females show a lower respiratory exchange ratio (RER) than males during submaximal endurance exercise, which translates into a proportionately lower carbohydrate and higher fat oxidation. Data from rodents show that 17-beta-estradiol may mediate these metabolic differences. 17-beta-estradiol supplementation in humans is less convincing; however, two studies found a reduction in glucose rate of appearance during exercise. No difference is found between genders in muscle glycogen content; however, lipid content in muscle is higher in females. Evidence shows that short chain OH-acyl CoA-dehydrogenase (SCHAD) maximal enzyme activity is higher in females. The rate of leucine oxidation is lower in females at rest and during endurance exercise. This is not apparently related to gender differences in branched chain-2-oxo-dehydrogenase (BCOAD) activity in skeletal muscle, which may implicate hepatic control. Important muscle proteins to examine in future research are hormone sensitive lipase, the enzymes of beta-oxidation, and fatty acid transporters.