The selection and utilisation of metabolic substrates during endurance exercise are regulated by a complex array of effectors. These factors include, but are not limited to, endurance training and cardiorespiratory fitness, exercise intensity and duration, muscle morphology and histology, hormonal factors and diet. Although the effects of these factors on substrate utilisation patterns are well understood, the variation in substrate utilisation during endurance exercise between males and females is not. Because of the extreme heterogeneity in exercise protocols and individuals studied, the differences in substrate utilisation between males and females remain somewhat inconclusive. Regardless of heterogeneity, if the results from studies are interpreted collectively, an apparent gender difference in the selection and metabolism of substrates can be seen in sedentary individuals. However, this difference between genders diminishes as the level of cardiorespiratory fitness is increased to that of highly trained individuals. During rest and lower intensity exercise, the preferential metabolism of lipid occurs with a concomitant sparing of muscle glycogen. However, as the intensity of exercise is increased, the relative contribution of carbohydrate also increases. The exercise intensity at which the shift from lipid to carbohydrate is determined and regulated by the previously mentioned factors. Because the intensity and duration of exercise play a predominant role, the variation in exercise protocols poses a methodological concern when interpreting previous research. When attempting to compare the metabolism of substrates during endurance exercise, appropriate selection and interpretation of measurement techniques are necessary. Measurement techniques include the nonprotein respiratory exchange ratio, muscle and fat biopsies and the measurement of various blood metabolites, such as free fatty acids and glycerol. Similarly, in vitro analysis of lipolytic activity has also been demonstrated in males and females in response to varying levels of female gonadotrophic hormones. When comparing the substrate utilisation patterns between males and females, the area of hormonal regulation has received less attention. Often the catecholamine response to endurance exercise is measured; however, the gonadotrophic hormones, particularly those of the female, have received less attention when comparing genders. Indeed, the regulatory nature of the female gonadotrophic hormones has been demonstrated. Collectively, the effects of elevated estrogen, as in the luteal phase of menstruation, appear to promote lipolytic activity. Estrogen-mediated lipolytic activation occurs by apparently altering the sensitivity to lipoprotein lipase and by increasing the levels of human growth hormone (somatropin), an activator of lipolysis. Similarly, lipolytic activity appears to decrease under situations of lower estrogen levels (i.e. during the follicular phase of menstruation and in males). In addition, other cellular mechanisms which may influence substrate utilisation include the response of the insulin receptor to varying levels of female gonadotrophic hormones. Insulin binding capacity is decreased in response to elevated levels of estrogen. Parallel to the regulatory effects of the female gonadotrophic levels is the menstrual status of endurance-trained females. When females progressively increase training volume, menstrual dysfunction becomes increasingly apparent. Thus, those females classified as endurance trained may vary in menstrual function from eumenorrhoeic to oligomenorrhoeic to ultimately amenorrhoeic. Since menstrual dysfunction may accompany endurance training, the circulating levels of female gonadotrophic hormones diminish to abnormally low levels. In response to subnormal levels of gonadotrophic hormones, the metabolism of energy substrates will probably change. Additional areas that may influence substrate utilisation include muscle morphology and histology. However, differences in the metabolic selection of substrates between genders do not appear to be appreciably affected by these variables. In terms of fibre type distribution, muscle morphology is similar between males and females. Although males have a tendency to retain greater muscle fibre diameter, the overall fibre type distribution is comparable between similarly trained males and females. Males reportedly have slightly higher succinate dehydrogenase enzyme activity regardless of training status. However, malate dehydrogenase activity is similar between genders. Therefore, it appears that muscle enzyme activity is more affected by training status than by gender. Furthermore, when matched for cardiorespiratory fitness level, males and females show few appreciable differences. When considering whether there are differences between males and females in terms of the selection and utilisation of metabolic substrates during exercise, numerous factors are involved: research methodology, training status, muscle morphology and histology, particularly endocrine function.