There is anecdotal evidence that bone strains may increase to the point that bone becomes susceptible to rapid failure when muscles become fatigued. To determine whether neuromuscular response could be a factor in accelerating bone failure, we tested the hypothesis that muscle fatigue causes a significant increase in peak principal and shear strains in bone. Ten adult foxhounds were subjected to rigorous exercise that caused muscular fatigue while myoelectrical activity of the quadriceps and hamstrings and strain on the distal tibia were monitored simultaneously. Ground reaction forces on the dog hindlimbs were measured before and after strain gauges had been applied to the tibia. The data show a significant shift to lower median myoelectrical frequencies in the quadriceps, indicating muscular fatigue, following the 20 min exercise period. In conjunction with this shift, peak principal and shear strains increased on both compressive and tensile cortices of the tibia and shear strain on the tensile cortex increased significantly (P = 0.02). The largest changes were along the anterior and anterolateral surfaces of the tibia, where peak principal strain increased by an average of 26-35% following muscular fatigue. The cross-sectional strain distribution was calculated at the gauge site at peak strain at the beginning of the exercise period and at peak strain after 20 min of exercise. These data show a change in strain distribution when muscle becomes fatigued. Strains on the posterior cortex of the bone showed the greatest change. Correlation analysis demonstrated a significant inverse association between median myoelectrical frequency and bone strain after 20 min of exercise (Spearman r² = 1.00;​ P = 0.05). These data show that muscle fatigue may be associated with increased bone strain.