The presence of the membrane attack complex of complement (MAC) was studied by a two-step immunofluorescence method in 15 patients with leukocytoclastic vasculitis of the skin, using an antibody against MAC neoantigen. Perivascular deposits of MAC were present in 13 specimens of lesional skin and only two specimens of clinically uninvolved skin, suggesting a possible pathogenetic role for MAC in the development of a skin lesion. Control studies were performed on the clinically normal skin of 15 individuals (11 patients with various nonbullous skin diseases and four healthy volunteers) and on skin lesions of seven patients with inflammatory skin diseases. In the clinically normal skin of only one patient, perivascular deposits of MAC were detected. This patient had rheumatoid arthritis and a cutaneous eruption due to the administration of aurothioglucose. We conclude that the activation of the terminal components of the complement system may play an important role in the formation of lesions in leukocytoclastic vasculitis of the skin, but is not an indispensable condition.