In addition to activity-induced lower leg pain, athletes with chronic compartment syndrome often have neurologic symptoms, including weakness and numbness of the lower leg and foot. Animal research has documented that compartment pressures >30 mm Hg result in partial nerve conduction block. The deep peroneal motor, superficial peroneal sensory, and tibial nerves run through the anterior, lateral, and deep posterior compartment, respectively, and their electrophysiologic function can be measured using nerve conduction studies. The objective of this research was to determine whether nerve conduction studies could be used as noninvasive diagnostic tests for chronic compartment syndrome. Six subjects with chronic compartment syndrome symptoms, including activity-induced weakness and/or numbness of the lower leg and/or foot, were observed. Each subject underwent the following bilateral pretreadmill and postreadmill running investigations: pressure measurements of the anterior, lateral, and deep posterior compartments; and nerve conduction studies of the deep peroneal motor, superficial peroneal sensory, and tibial motor nerves. Twelve of the 36 compartments tested had abnormally high postexercise pressures (>35 mm Hg). However, no exercise-induced impairment of function was found of the nerves within compartments with high pressures as compared to those of normal pressure. Similarly, no correlation was found between postexercise changes in electrophysiologic function and compartment pressure. Two subjects had electrophysiologic abnormalities suggestive of entrapment neuropathy of the superficial peroneal sensory nerve. These results indicate that nerve conduction studies are not useful in identifying chronic compartment syndrome of the lower leg. Their usefulness appears to be restricted to identifying lower-extremity peripheral nerve entrapments that can mimic chronic compartment syndrome.