Chicks fed a semisynthetic basal diet deficient in selenium and vitamin E for 14 to 22 days developed skeletal myodegeneration and exudative diathesis. Chicks fed the basal diet supplemented with either 0.2 ppm of selenium (as selenite) or 100 IU alpha-tocopherol acetate/kg were protected from deficiency disease, but chicks fed the basal diet plus 0.4% L-cystine were not protected. Pectoral muscles of deficient chicks were red and edematous. Light and electron microscopic study of affected muscles revealed fibers with hyaline and granular degeneration. In hyalinized fibers, the initial ultrastructural alterations were increased density of the sarcoplasm and myofibrils, dilatation of sarcoplasmic reticulum, formation of subsarcolemmal vacuoles, and disruption of mitochondrial membranes. In later stages, alterations in these fibers included myofibrillar disruption and lysis, nuclear pyknosis and lysis, disruption of the plasma membrane with persistence of basal lamina and scattered adhering satellite cells, and eventual invasion by macrophages. In fibers with granular degeneration, the ultrastructural observations included decreased density of the sarcoplasm, prominent mitochondrial swelling and distortion, and multiple foci of myofibrillar lysis that eventually coalesced to produce generalized lysis. Prominent vascular lesions associated with exudative diathesis were present in degenerated muscle but were not considered to precede development of fiber alterations. Affected blood vessels had endothelial cells with mitochondrial damage and accumulations of cytoplasmic dense bodies and areas of endothelial disruption with adhering fibrin thrombi.