The interrelationship between lymphocytes and hepatocytes was examined by light and electron microscopy, using epoxy-resin embedded thick and thin sections of biopsy liver tissues from patients with chronic persistent hepatitis (CPH) and chronic active liver disease (CALD). Close apposition of lymphocytes with hepatocytes was classified according to morphologic features produced by surface contact, invagination, direct penetration, and aggregation. Lymphocytes in biopsy specimens from patients with CALD showed these morphologic patterns much more frequently than in those from patients with CPH. These small, infiltrating lymphocytes established intimate contact with hepatocytes through their multiple-surface projections. Hepatocyte degeneration appeared to occur in association with the structural contact. The morphologic association of lymphocytes with hepatocytes in CALD is consistent with the participation of cell-mediated immune processes.