Long-term aerobic exercise and energy intake regulate body composition in a complex manner. To study the combined effects of exercise and energy restriction on muscle mass, we measured skeletal and cardiac muscle protein synthesis after 28 days of two levels of energy restriction with or without daily running-wheel exercise in female rats. Protein synthesis was measured as H-3-Phe incorporation 10 minutes' postbolus of a flooding pulse injection. The two exercise plus energy-restriction groups had greater skeletal muscle and cardiac muscle mass compared with their food-matched groups. Cardiac, gastrocnemius, and soleus muscle protein synthetic rates were proportional to their muscle masses. Exercise-induced energy deficits preserved cardiac and soleus mass to a greater extent than gastrocnemius mass, whereas the effects of energy restriction were similar in all three muscles. These findings suggest that energy intake and exercise have independent effects on the regulation of muscle mass and protein synthesis. Copyright (C) 1995 by W.B. Saunders Company