ExtractIn an effort to characterize the hepatic abnormality in patients with α1-antitrypsin deficiency, three unrelated children with the disorder (Pi types ZZ and SZ), two heterozygous parents (Pi type MZ), and three normal subjects (Pi type MM) were studied. As expected, the livers of the ZZ- and SZ-deficient subjects showed abnormal accumulation of α1-antitrypsin in the cisternae of the rough endoplasmic reticulum as judged by immunofluorescent and electron microscopic studies. Their parents (MZ phenotype) demonstrated identical although less extensive hepatic abnormalities. Short term cultures of liver tissue in the presence of radiolabeled amino acids showed both synthesis and release of α1-antitrypsin in normal control subjects and in the patients with the Z protein. Radiolabeled intracellular α1-antitrypsin could not be found. These studies demonstrate synthesis of α1-antitrypsin by the livers of normal and genetically deficient subjectsin vitro, and suggest several possible mechanisms for α1-antitrypsin deficiency.SpeculationStudiesin vitroof the synthesis and release of α1-antitrypsin, as shown in the present investigation, may reveal the molecular basis of this genetic disorder.