Muscular fatigue is a common complaint in patients undergoing radiation therapy. In total-body irradiated animals in which extreme degrees of muscular weakness are observed, creatinuria appears to resemble in mechanism that found in muscle-wasting disorders, e.g., muscular dystrophy. The 24-hour urinary creatine and creatinine and the fatigue symptomatology of 14 patients undergoing radiation therapy were determined before and at weekly intervals during and after treatment. The degree of creatinuria might be related to the anatomical site of irradiation and to the amount of radiation absorbed, particularly to the amount of muscle mass irradiated. The severest fatigue symptoms were observed in patients with the greatest degree of creatinuria. The various mechanisms or factors influencing creatinuria were considered.