Serum CPK levels were determined in a series of 94 patients with amyot-rophic lateral sclerosis. CPK levels were elevated in 75.5 percent of the patients, and were highest in those who had the disease for 3 to 15 months. Men had significantly higher CPK levels than women. Levels were significantly higher in patients showing a combination of denervation atrophy and myopathic changes in the muscle than in patients with denervation atrophy alone. However, the higher CPK values in the former group lost statistical significance with prolonged duration of the disease. There was regression of the CPK levels with longer duration of the disease that showed significant negative correlation. It is concluded that one of the important factors contributing to increased CPK activity in amyotrophic lateral sclerosis is associated myopathic changes found in the muscles.