Support for the hypothesis that biogenic amines are involved in the production of muscle diseases comes from a report that rat muscle is damaged by combining distal aortic ligation with serotonin injection. Our studies explore the role of serotonin in the production of the myopathic changes in the aortic ligation-serotonin model. Twenty-six young Sprague-Dawley rats were subjected either to aortic ligation alone, aortic ligation followed by injection of serotonin (40 mg/kg, i.p.), or injection of serotonin alone. Following sacrifice 7--14 days later, 10 micrometer frozen sections of the soleus muscle were stained by trichrome, NADH-TR, and ATPase methods. Focal necrosis and phagocytosis or focal regeneration were seen after aortic ligation with, or without, subsequent serotonin injection. Serotonin alone produced only occasional mild changes in muscle. Therefore, we conclude that the significant damage to muscle in the ligation-serotonin model is provided by the aortic ligation, not the serotonin injection.