Childhood dermatomyositis is a distinct subset of dermatomyositis with highly variable outcome. We reviewed our experience with 29 patients observed over a period of 22 years and attempted to correlate tissue manifestations with outcome. Distinctive vascular lesions included non-necrotizing lymphocytic vasculitis and a unique spectrum of endovascular injury producing temporary or permanent occlusion of small arteries and capillaries. Vessels with noninflammatory endovasculopathy were often reactive with fluorescein-conjugated antisera to IgM, C3d, and/or fibrin. Lesions linked to endovascular injury include infarction, zonal myopathy, and loss of capillary network. We were able to identify half of the children destined to have persistent morbidity on the basis of severity of vasculopathy in pretreatment muscle-biopsy specimens. Our observations support a central role for endothelial cell injury in the pathogenesis of childhood dermatomyositis, suggest a basis for assessing the efficacy of therapy, and provide a focus for investigation of basic mechanisms.