Abstract Segal RL, Song AW. Nonuniform activity of human calf muscles during an exercise task. Objectives To determine the distribution of leg muscle activity during heel raises using magnetic resonance imaging (MRI) with special emphasis on quantifying activity across multiple axial sections and to determine if there are differences among portions of active muscles. Design Pre- and postexercise (heel raise) T2-weighted time measurements were assessed by using repeated-measures analysis of variance (ANOVA) and t tests. Setting Laboratory and MRI suites. Participants Eight healthy volunteers. Intervention Unilateral heel raises every 2 seconds for at least 60 seconds. Main Outcome Measures Percentage changes from T2-weighted magnetic resonance images of the lateral gastrocnemius, medial gastrocnemius, peroneus longus, soleus, and tibialis anterior muscles, across 10 axial sections, exercise bouts, and a pre-exercise condition. Results The lateral gastrocnemius, medial gastrocnemius, peroneus longus, and soleus had significantly larger changes in T2 time from pre-exercise times than did the tibialis anterior for whole muscles as determined by using repeated-measures ANOVA and post hoc analyses. The medial gastrocnemius had a significantly greater change in T2 time than the lateral gastrocnemius. Proximal axial sections of the lateral gastrocnemius, medial gastrocnemius, and soleus had significantly larger changes in T2 time from pre-exercise than did distal sections. Conclusions This work reconfirms that multiple muscles contribute to plantarflexor forces and additionally shows an apparent proximal versus subvolume organization of activity within the gastrocnemius, medial gastrocnemius, and soleus but not the peroneus longus. This proximal versus distal organization of muscle activity needs further investigation. There may be clinical implications for therapeutic interventions that require accurate placement of electrodes such as biofeedback.