The diagnosis of Weber-Christian disease was made by clinical and histopathologic findings in a 25-year-old woman who had recurrent nodules on the legs and arms. The patient's history also disclosed multiple episodes of swelling trauma. Histopathologic examination of the lesions showed a prominent vasculitis. Studies of serum complement and kallikrein levels and of the fibrinolysis-clotting system showed a decrease in the levels of C3, C4, and total hemolytic complement activity and deficiencies (less than 20% of the normal values) of alpha 1-antitrypsin (alpha 1-AT) and antichymotrypsin activity. Chemical analyses of the patient's alpha 1-AT indicated a PiZZ genotype. Intermediate values of both inhibitor levels were detected in six family members. It is assumed that protease-inhibitor deficiencies predispose the development of panniculitis and vasculitis on trauma.