To evaluate the immune process involved in the pathogenesis of liver cell damage in chronic hepatitis delta virus infection, a panel of monoclonal antibodies against pan T cells (Leu 4), inducer/helper T cells (Leu 3a+3b), suppressor/cytotoxic T cells (Lue 2a), B cell (Leu 12), monocyts/macrophages (Leu M3) and NK/K cells (Leu 7) was used to characterize the subsets of the mononuclear cell infiltrates in livers from 12 patients with chronic type D hepatitis, with special emphasis on the areas of periportal piecemeal necrosis and intralobular necrosis. A control group of 12 patients with chronic type B hepatitis was also studied for comparison. The results revealed that the livers from patients with chronic type D hepatitis showed a prominent mononuclear cell infiltration in portal/periportal and intralobular areas. Furthermore, the vast majority of the mononuclear cell infiltrates in liver were T cells, which constituted more than 80% of the cells in the areas of periportal piecemeal necrosis and intralobular necrosis and about 60% of the cells in the portal tract, whereas B cells, monocytes/macrophages and NK/K cells were relatively uncommon. Among T cell populations, the inducer/helper T cells were predominant in the portal tract, and, by contrast, the suppressor/cytotoxic T cells were predominant in the areas of piecemeal necrosis and intralobular necrosis. The distribution of the mononuclear cell subsets in relation to the different topographical areas of the liver in patients with chronic type B hepatitis was essentially the same as that observed in chronic type D hepatitis. Our findings therefore suggest that T cell-mediated immunity might play a role in the pathogenesis of chronic type D hepatitis, similar to that suggested for chronic type B hepatitis.