Since proteolytic processes are prominent in psoriasis, sera of forty-five psoriatics were examined for alpha 1-antitrypsin (alpha 1-AT) phenotype and eighteen sera, for alpha 1-AT content and function. Five sera (11.1%) had heterozygous phenotypes (2 MZ and 3 MS), a prevalence of Z and S variants similar to that reported in nonpsoriatic populations. Two of three variants examined for content and function exhibited marked reductions. Since MZ heterozygotes are almost always, and MS phenotypes sometimes, associated with decreased serum alpha 1-AT levels, and since Z and MZ phenotypes are associated with increased hepatic fibrosis or cirrhosis, these variants may be relevant to problems of spontaneous fibrosis or methotrexate-induced hepatotoxicity in psoriasis. alpha 1-AT deficiency may also contribute to guttate flares with infection and to increased O-2 . production by psoriatic sera-stimulated polymorphonuclear leukocytes (PMNs). Although no evidence exists that psoriasis is more prevalent among persons with hypomorphic alpha 1-AT phenotypes, such defects may contribute to severity of inflammation and hyperplasia.