Alpha-interferon (IFN-alpha) has been shown to be beneficial in the treatment of chronic active hepatitis occurring as a consequence of hepatitis B virus (HBV) infection. Therefore, it has been used to reduce the high rate of allograft infection in clinical liver transplantation of HBV-positive individuals. This study was performed to evaluate the effect of IFN-alpha on lymphocyte subsets as well as the HLA-DR antigen expression in liver tissue. The resected livers obtained from two groups of patients who received liver transplants between 1983 and 1987 at the University of Pittsburgh were examined: group A consisted of 11 patients who were not treated (controls), and group B consisted of 10 patients (experimental group) who were treated with IFN-alpha for 29.4 +/- 5.6 days prior to transplantation. No differences between the two groups existed in terms of a variety of demographic and clinical characteristics. Both groups had cirrhosis as a result of chronic HBV infection. Monoclonal antibodies to cell-surface antigens unique to different lymphocyte populations and the HLA-DR antigens were used in conjunction with the avidin-biotin-immunoperoxidase technique to identify cells in tissue sections. The number of HLA-DR-positive lymphocytes in the liver was increased (P less than 0.005) within the portal areas in rIFN-alpha-treated group as compared to that seen in the untreated group (84.4 +/- 13.6/HPF vs 33.3 +/- 4.8/HPF). Moreover, the intensity of the HLA-DR antigen expression in the portal areas (P less than 0.02) and in the hepatic lobule (P less than 0.05) was greater in the treated group than in untreated group.(ABSTRACT TRUNCATED AT 250 WORDS)