No investigation has previously reported activation of satellite cells in vivo in human muscle after a single bout of high intensity exercise. Eight individuals performed a single bout of high intensity exercise on one leg, with the contralateral leg being the control. A significant increase in mononuclear cells staining for N- CAM and fetal antigen 1 (FA1) were observed within the exercised human vastus lateralis muscle at day 4 and 8 post exercise. In addition, a significant increase in the concentration of the FA1 protein was determined in intramuscular dialysate samples taken from the vastus lateralis muscle of the exercising leg (Day 0: 1.89 ± 0.82 ng.ml-1; Day 2: 1.68 ± 0.37 ng.ml-1; Day 4: 3.26 ± 1.29 ng.ml-1, P<0.05 versus basal; Day 8: 4.68 ± 2.06 ng.ml-1, P<0.05 versus basal and control) with no change being noted in the control leg. Despite this increase in N-CAM and FA1 positive mononuclear cells, an increase in the expression of myogenin and the MHCneonatal was not observed. Interestingly, myofibre lesions resulting from extensive damage to the proteins residing within the myofibre, particularly, desmin or dystrophin, was not required to induce the expression of both N-CAM and FA1. We therefore propose that satellite cells can be induced to re-enter the cell cycle after a single bout of unaccustomed high intensity exercise however this stimulus is not sufficient for the cell to undergo terminal differentiation without a further exercise stimulus.