Objective: To study the effects of foot orthotics on the mean electromyographic amplitude of proximal and distal lower extremity muscle groups during the first 50% of the stance phase during treadmill running. Design: Repeated measures. Setting: Subjects were recruited from the general community. Participants: Twelve recreational runners who were symptomatic for lower extremity pain. Clinical and radiographic findings confirmed the presence of structural malalignment of the foot. Intervention: Semirigid orthotics were fabricated for each subject, and like footwear provided. Main Outcome Measures: Surface electromyogram activity from the tibialis anterior, medial gastrocnemius, vastus medialis, vastus lateralis, and biceps femoris was collected during treadmill running at self-selected speeds for orthotic and nonorthotic conditions. Root mean square values were averaged across 10 cycles, normalized to time and expressed as a percentage of the nonorthotic condition. Results: Paired t test results showed statistically significant changes (p < .05) for the biceps femoris (-11.1%) and tibialis anterior (+37.5%) muscle groups during the orthotic condition. Electromyographic activity in the medial gastrocnemius, vastus medialis, and vastus lateralis with orthotic use was not significantly different from the nonorthotic condition. Conclusion: Although subjects' electromyographic responses to orthotic use were highly individualized, the findings of this study may enhance our understanding of muscle activity changes associated with positive outcomes from orthotic use.