A number of studies have examined the functional roles of individual muscles during normal walking, but few studies have examined which are the primary muscles that respond to changes in external mechanical demand. Here we use a novel combination of experimental perturbations and forward dynamics simulations to determine how muscle mechanical output and contributions to body support and forward propulsion are modulated in response to independent manipulations of body weight and body mass during walking. Experimentally altered weight and/or mass were produced by combinations of added trunk loads and body weight support. Simulations of the same experimental conditions were used to determine muscle contributions to the vertical ground reaction force impulse (body support) and positive horizontal trunk work (forward propulsion). Contributions to the vertical impulse by the soleus, vastii and gluteus maximus increased (decreased) in response to increases (decreases) in body weight; whereas only the soleus increased horizontal work output in response to increased body mass. In addition, soleus had the greatest absolute contribution to both vertical impulse and horizontal trunk work, indicating that it not only provides the largest contribution to both body support and forward propulsion, but the soleus is also the primary mechanism to modulate the mechanical output of the leg in response to increased (decreased) need for body support and forward propulsion. The data also showed that a muscle's contribution to a specific task is likely not independent of its contribution to other tasks (e.g., body support vs. forward propulsion).