Objective. To determine the kinematic, kinetic and EMG responses to perturbations of the foot by running in varus, neutral, and valgus-wedged shoes. Design. Within-subjects study comparing kinematics, kinetics and EMG while running in three different shoe conditions. Background. Excessive pronation has been cited as a key contributor to many types of running injuries. However, the roles of the extrinsic foot muscles (those that control motion of the foot) during the stance phase of running have not been adequately identified, which is critical to determining the relationship between pronation and injury. Methods. Ten males ran in varus, valgus, and neutral-wedged shoes while three-dimensional kinematic and kinetic data and EMG data were collected. Surface EMG data were collected from the tibialis anterior, peroneus longus, medial and lateral gastrocnemius, and soleus. Indwelling EMG was obtained from the tibialis posterior. The net joint moment, power, and total positive and negative work was calculated in the frontal plane. EMG onset, offset, and integrated values were reported. Results. The maximum eversion angle, maximum inversion moment and total negative work done in the frontal plane were greatest while running in the valgus shoe and least in the varus shoe. The greater joint moment was not accompanied by changes in muscle activation patterns, although the tibialis posterior data were inconclusive in this respect. Conclusions. Greater pronation leads to greater energy absorption in the foot invertor muscles and tendons. While not conclusive, the EMG data suggest that for these muscles there was not a neuromuscular adaptation to the perturbation. Relevance This study reinforces the hypothesized link between excessive pronation and injury and provides valuable insight into the muscular responses (or lack thereof) when foot motion is altered. This information is critical in understanding the effects of shoe design and orthotic interventions.