Dermatomyositis (DM) is a complement-mediated microangiopathy affecting skin and muscle resulting in skin abnormalities, including subcutenous calcifications, muscle weakness and disability. The disease generally responds to steroids or immunosuppressive drugs, but a number of patients are resistant or partially responsive to these therapies, prompting us to examine the efficacy of IVIg. A double-blind placebo-controlled study demonstrated that IVIg is very effective in improving both the muscle strength and the skin rash. The clinical benefit, which was impressive in patients with early disease, was associated with improvement in the muscle cytoarchitecture. Quantitative histological studies in repeated muscle biopsies showed a statistically significant increase in the size of muscle fibers and the number of capillaries with normalization of the capillary diameter. Resolution of the aberrant immunopathological parameters, including interception of complement activation products and downregulation of T cells, ICAM-I, VCAM, TGF-beta and MHC-I molecules, was also noted. Further, a number of immunoregulatory and structural genes were modified in the patients' muscle biopsies after therapy. The study concluded that IVIg is an effective second-line therapy for patients with DM incompletely responding to steroids.