A novel monoclonal antibody (mAB) TIA-1, which recognizes a 15-kd granule-associated protein of cytotoxic T lymphocytes and natural killer cells, has been applied to sections of lymph nodes with human immunodeficiency virus (HIV)-induced lymphadenopathy (follicular hyperplasia and lymphocyte depletion). The protein recognized by this mAB induces apoptosis in permeabilized lymphocytes in vitro. While this mAB reacted with approximately 46% of paracortical CD8+ cells in control nodes, it reacted with 75% of such cells in HIV-induced follicular hyperplasia. Germinal centers of the control nodes contained few TIA-1+ cells; in follicular hyperplasia caused by HIV-1, almost all germinal center CD8+ cells were TIA-1+. Both in the control nodes and in HIV-induced follicular hyperplasia the majority of TIA-1+ cells coexpressed CD45R0. A marked loss of CD8+ TIA-1+ cells was seen in lymphocyte-depleted nodes of patients with AIDS. The loss of these cytotoxic T lymphocytes may have a significant impact on the progression of the disease.