The expression of activated cell antigens (Ags) on adult T cell leukemia (ATL) cells at different clinical stages (acute, chronic, and smoldering), and ATL cells from enlarged lymph nodes were studied using monoclonal antibodies (MoAbs). The expressions of CD25 (Tac), CD28, T9 (transferrin receptor), and Ki-67 (proliferating cell nuclear antigen) Ags were high, and that of CD7 Ag was low in both acute and chronic ATL cells compared with that in normal T cells. The expressions of T9 and Ki-67 Ags were higher in acute ATL cells than in chronic ATL cells. The expression of CD38 Ag was higher in acute ATL cells but not in chronic ATL cells compared with normal T cells. On the contrary, the expression of HLA-DR Ag on the cell surface and the transcript of the HLA-DR Ag gene were high in chronic ATL cells, but not in acute ATL cells. A high percentage of lymph node ATL cells expressed T9, CD38, and Ki-67 Ags, although the peripheral blood ATL cells of the same patients showed significantly lower levels of expression of the same Ags. Interestingly, CD7 and HLA-DR Ags were detected on the majority of lymph node ATL cells. Moderately high percentage of smoldering ATL cells expressed CD25, CD28, and HLA-DR Ags, though a few numbers of leukemic cells were present in the samples. These findings confirm that the modes of activation of ATL cells in different clinical stages differ, and suggest that the differences might be reflected in the clinical features. The low expression of HLA-DR Ag in acute ATL cells, despite high expression of the Ag in chronic ATL cells, suggests that successive events that suppress HLA-DR Ag expression are necessary for the transformation of chronic ATL cells into acute ATL cells. Moreover, the high expressions of T9, CD38, Ki-67, CD7, and HLA-DR Ags on lymph node ATL cells indicate that ATL cells preferentially proliferate in lymph nodes.