An integrative analysis, comprising radiographic imaging of the foot, plantar pressure measurements, surface electromyography (EMG) and finite element (FE) modelling of the three-dimensional (3D) foot structure, was used to determine the effects of muscular fatigue induced by intensive athletic or military marching on the structural stability of the foot and on its internal stress state during the stance phase. The medial/lateral (M/L) tendency towards instability of the foot structure during marching in fatigue conditions was experimentally characterised by measuring the M/L deviations of the foot-ground centre of pressure (COP) and correlating these data with fatigue of specific lower-limb muscles, as demonstrated by the EMG spectra. The results demonstrated accelerated fatigue of the peroneus longus muscle in marching conditions (treadmill march of 2 km completed by four subjects at an approximately constant velocity of 8 km h(-1)). Severe fatigue of the peroneus longus is apparently the dominant cause of lack of foot stability, which was manifested by abnormal lateral deviations of the COP during the stance phase. Under these conditions, ankle sprain injuries are likely to occur. The EMG analysis further revealed substantial fatigue of the pre-tibial and triceps surae muscles during intensive marching (averaged decreases of 36% and 40% in the median frequency of their EMG signal spectra, respectively). Incorporation of this information into the 3D FE model of the foot resulted in a substantial rise in the levels of calcaneal and metatarsal stress concentrations, by 50% and 36%, respectively. This may point to the mechanism by which stress fractures develop and provide the biomechanical tools for future clinical investigations.