In dermatomytosis, humorally-mediated damage to muscle and skin microvasculature appears very important. The deposition of the membrane attack complex (C5-9) on the capillaries has been shown to precede the destruction of muscle fibers and to be a specific finding in the skin lesion. These observations, along with the recent discovery of the effectiveness of intravenous gammaglobulin (IVIG) in dermatomyositis, support the role of complement activation in the pathogenesis of dermatomyositis. Among the activated components of the complement system, the products that are generated after cleavage of C5, namely, C5a and C5b-9, are potent inflammatory mediators with pleiotropic activities. Inhibition of complement activation at C5 would prevent the formation of these pro-inflammatory molecules while allowing the generation of C3b, which is critical for opsonization and immune complex clearance. C5 inhibition therefore represents a potentially effective therapeutic modality for dermatomyositis.