Liver cell ultrastructure was studied in 6 adult patients with α1-antitrypsin (AAT) deficiency (Pi phenotype ZZ); all except 1 were suffering from severe pulmonary emphysema; the liver was histologically normal in 3 patients, and portal fibrosis or cirrhosis was present in the other 3. Conventional electron microscopy showed specific changes consisting of deposits of an amorphous material in the dilated lumina of the endoplasmic reticulum; although these changes were demonstrated in all specimens, the number of liver cells showing these abnormalities varied markedly with each patient; the other liver cells were normal or were affected by nonspecific changes consisting mainly of an increased number of lysosomes; the liver cells with these nonspecific changes were present only in the patients with liver fibrosis or cirrhosis. Electron microscopy, combined with the use of anti-AAT antibodies labeled with horseradish peroxidase, demonstrated that a material antigenically similar to AAT was present in the deposits and on the ribosomes of the endoplasmic reticulum of those liver cells with the specific ultrastructural changes. It is concluded that in patients with AAT deficiency: (1) a material antigenically similar to AAT is synthesized by the ribosomes, but, for unknown reasons, is not exported or is poorly exported into plasma and accumulates in the lumina of the endoplasmic reticulum; (2) the nonspecific ultrastructural changes, associated with, and presumably leading to, liver fibrosis and cirrhosis, are not directly related to the accumulation of this material in the liver cells.