It has been demonstrated experimentally that the bullae observed in autoimmune pemphigus are due to the action of proteases. So far, no case of pemphigus associated with deficiency in antiprotease has been reported. We present a case of pemphigus associated with familial deficiency in alpha 1-antitrypsin (alpha 1-AT), a major human body antiprotease. A 35-year old man presented with pemphigus preceded during 18 months, and accompanied by pruritus. The lesions were polymorphous, being made of solitary bullae, circinate vesiculobullae and squamous scabie plaques. Histopathological examination showed an intraepidermal bulla with acantholysis, a very spongiosis. The diagnosis of autoimmune pemphigus was confirmed by fluorescence of the epidermis in IgG and C3 and by the presence of antibodies directed against the intracellular substance. The initial treatment, which consisted of prednisolone 10 mg/kg/day and 10 plasma exchanges, was rapidly successful, but several relapses occurred thereafter. Two years after the pemphigus was diagnosed, a panlobular emphysema was discovered which made it possible to demonstrate a severe familial deficiency in alpha 1-AT of the Pi phenotype. This is the first published case of alpha 1-AT deficiency associated with autoimmune pemphigus. In our patient the skin disease presented as herpetiform pemphigus (initial features of dermatitis herpetiformis, followed by misleading polymorphous lesions, rare acantholytic cells, good response to corticosteroids), but there was no eosinophilic spongiosis. The frequency of alpha1-AT deficiency (estimated at 1 in 1,000 in northern Europe) and the lack of published cases with such an association may suggest a pure coincidence.(ABSTRACT TRUNCATED AT 250 WORDS)