Alpha-1-antitrypsin (AAT) is a serum glycoprotein that inhibits the action of proteases such as trypsin. The normal allele is PiM; the most common mutations include PiS and PiZ. Heterozygotes PiMS and PiMZ have some risk for liver and lung disease. Patients with PiZZ, PiSS, and PiSZ are at increased risk. Deficiency of AAT has been associated with the early onset of panlobular emphysema in adults. Liver diseases in both children and adults can also occur. Children with AAT may present with neonatal hepatitis or with cirrhosis developing during the second year of life or later. Adults with AAT deficiency may have normal livers, may develop chronic active hepatitis, or may have cirrhosis. The distinctive histologic finding in cases of AAT deficiency is the presence of small round red globules in liver cells near portal tracts or fibrous septae. These globules stain strongly with PAS, as shown here, and have been shown to consists of material antigenically related to AAT. The pathogenesis of these globules and the relationship to the development of liver disease is unclear.