We have studied the clinical histories and liver biopsy findings in 1951 consecutive adult patients with suspected chronic liver disease, and in four known PiZ-homozygous alpha 1-antitrypsin-deficient patients with emphysema (candidates for lung transplant) and no known liver disease, in order to assess the importance of periportal alpha 1-antitrypsin granules in the liver and their possible causal role in liver disease, and to assess the value of possible screening tests. Periportal granules were found in 30 (1.5 per cent) of the 1951 liver biopsies and in all four known PiZ-homozygous subjects. They were the sole putative aetiological agent in eight of 85 patients (9.4 per cent) with otherwise cryptogenic cirrhosis and present in 2.5 per cent of patients with cirrhosis of known aetiology (alcohol, autoimmune etc.). All but one were Z phenotype (seven homozygotes, 22 heterozygotes). alpha 1-Antitrypsin granules were seen in 12 patients (including three of four lung transplant candidates) with no histological chronic liver disease. Determination of serum alpha 1-antitrypsin levels was quite unhelpful in identifying these patients. This study does not support the concept that periportal alpha 1-antitrypsin granules are necessarily pathogenic, but in some cases they may be causally related to otherwise cryptogenic liver disease. The presence of granules gave no important diagnostic, therapeutic or prognostic information.