ABSTRACT— In order to determine the diagnostic value of α1-antitrypsin (AAT) globules as a morphological marker of AAT-deficiency of the Pi-Z type, liver needle biopsies from a prospective series of 600 patients were stained with PAS after pretreatment with diastase and by indirect immunoperoxidase staining for AAT deposits. Serum AAT phenotypes of the patients were determined by means of isoelectric focusing. Thirty-two biopsies were from patients with the Pi-Z allele (31 MZ, 1 Z), and 568 biopsies from patients without the Pi-Z allele. AAT globules larger than 3 μm were found in 16 biopsies of which 15 were from patients with the Pi-Z allele (diagnostic specificity 0.94), whereas 20 of 26 biopsies with AAT globules larger than 1 μm were from Pi-Z patients (diagnostic specificity 0.77). Only 47% of the biopsies from patients with the Pi-Z allele contained AAT globules larger than 3 μm. Thus, although AAT globules larger than 3 μm are highly specific as a morphological marker of the Pi-Z allele, their rather infrequent occurrence in carriers of the Pi-Z allele indicates that all investigations concerning the correlation between AAT deficiency of the Pi-Z type and liver disease should be based on phenotyping of sera from all the patients.