It has been reported that the severe complication of dengue virus infection, dengue hemorrhagic fever (DHF) is much more commonly observed during secondary dengue virus infections than primary infections. In order to elucidate the role of T lymphocytes in the pathogenesis of DHF, we attempted to determine whether T lymphocytes are activated in vivo during dengue virus infections, by examining the levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4), soluble CD8 (sCD8), interleukin-2 (IL-2) and interferon-'y (IFN'y) in the sera of 59 patients with DHF and 41 patients with dengue fever (DF).The levels of sIL-2R, sCD4, sCD8, IL-2, and IFNy were significantly higher in the acute sera of patients with DHF than in the sera of healthy children (P < 0.001 for all markers). The acute sera of patients with DF contained higher levels of sIL-2R, sCD4, IL-2, and IFN-y than the sera of healthy children (P < 0.001 for sIL-2R, IL-2, and IFN-y; P < 0.05 for sCD4), but did not have elevated levels of sCD8. The levels of sIL-2R (P < 0.05), sCD4 (P < 0.001), and sCD8 (P < 0.001) were higher in DHF than in DF on days 3-4 after the onset of fever. The levels of IL-2 and IFN'y in patients with DHF were highest 1 d before defervescence. There were no significant differences in the levels of sIL-2R, sCD4, sCD8, IL-2, and IFNy among grades 1, 2, and 3 of DHF. These results indicate (a) T lympho-