The phenotypes of infiltrating lymphocytes in liver with chronic hepatitis C, including changes associated with interferon (IFN) treatment, were characterized. Specimens obtained from 22 patients treated with IFN were examined using avidin-biotin-peroxidase immunohistochemistry. In areas of lobular and periportal inflammation, most lymphocytes were CD8+ T cells of the CD45RO+ (memory) subset. The centres of lymphoid follicles were occupied by CD20+ B cells and a few CD4+ T cells which were CD45RA+ (naive subset). Follicular centres were surrounded mainly with CD4+ T cells. CD8+ T cells, mostly CD45RO+, were scattered through the mantle zones of follicles and extended around them. No significant changes in CD45RA+ lobular infiltrates accompanied IFN treatment. On the other hand, the number of CD45RO+ lobular infiltrates decreased after IFN treatment in complete responders (P < 0.01). Moreover, there were significant correlations between CD45RO+ cell counts and serum alanine aminotransferase concentrations, CD45RO+ cell counts and the liver histologic grade and CD45RO+ cell counts and CD8+ cell counts. These results suggest that CD8+ memory T cells participate in hepatocyte injury in chronic hepatitis C, and that a decrease of CD8+ memory T cells correlates with the decreased liver inflammation with IFN treatment.