Contrary to our hypothesis, SP600125 supply circulating FGF21 was decreased following sprint interval training. In adult humans, previous studies have demonstrated increased circulating FGF21 following single bouts of exercise, greater magnitudes of increase in FGF21 following higher intensity exercise, and increased FGF21 after short-term of incremental treadmill exercise. In the acute exercise studies, blood was sampled one hour following exercise completion, and in the training study within 24-hours of the final exercise session. Recently, the half-life of FGF21 has been established as less than two hours in humans. In the present study, blood was sampled 48-hours after the final exercise bout; thus discrepancies between the present and previous studies may be attributable to FGF21’s short half-life and/or the duration for which its secretion was increased. b-Klotho is a member of the Klotho family of transmembrane proteins, is present in FGF21 target tissues, and is thought to be required for FGF21 mediated metabolic effects. Bidirectional FGF21 and b-Klotho responses to exercise and caloric restriction have been reported ; these responses were thought to mediate protection from obesity and obesity-induced nonalcoholic fatty liver disease in rats. Clearly the responses of, and interactions with, FGF21 to exercise training, including sprint interval training, are complex, and single time point studies may be inadequate to fully describe this physiology. Another novel finding of the present study was the sexual dimorphic response of circulating irisin to sprint interval training. Recent studies have reported no change in circulating irisin following aerobic and strength training programs and there were no differences in the responses to training between males and females. Explanations for this current sex difference are potentially related to differences in the transcription/translation of FNDC5 and/or the regulation of the cleavage, secretion, and/or clearance of irisin. Potential contributors include differences in body composition, variability in other adaptations to sprint interval training, and the influence of circulating sex hormones. With respect to body composition, large population studies that have included adults spanning a wide range of body composition have reported positive relations between circulating irisin and fat free mass. In the present study, fat free mass was lower in females compared with males but there was no relation between fat free mass and circulating irisin. Relative to these other studies, our research participants comprised a smaller and relatively homogenous population; this may explain the nonsignificant associations. With respect to the influence of sprint interval training on exercise tolerance, there was neither a main effect of sex nor an interaction between sex and training, suggesting that males and females benefitted similarly, at least from an athletic performance perspective, from the exercise regimen. Finally, we did not attempt to time standardize data collection relative to menstrual phase.