Brazilian pemphigus foliaceus is an autoimmune blistering skin disease of man that has a very high incidence in a confined geographical distribution. Rocket immunoelectrophoresis of plasma showed increased levels of complement fragments, C4d and Ba, indicating activation of complement through both the classical and the alternative pathways. Less sensitive methods such as CH50, total C3 and C4 did not demonstrate this activation, and immune complex measurements were within normal range. While complement may not be absolutely necessary for the development of skin lesions, our longitudinal studies show that activation of complement is at its highest during the most active phase of the disease.