Dengue viruses, of which there are four serotypes, are the most important arthropod-borne viral infections in the world, accounting for more than 250,000 cases of dengue hemorrhagic fever (DHF) and 10,000 deaths annually [Monath, 1994]. Infection with dengue viruses can yield different clinical syndromes, including (1) undifferentiated febrile illness, seen more commonly in children;(2) dengue fever (DF), a flu-like syndrome characterized by high fever, headache, retroorbital pain, myalgias, abdominal pain, nausea, and vomiting; and (3) dengue hemorrhagic fever (DHF), a plasma leak syndrome that, in its most severe form, can be life-threatening [Nimmannitya, 1987]. Plasma leakage is a major clinical feature of DHF and tends to occur around the time of defervescence. We have been interested in the events that precede the period of plasma leakage to better define its etiology. We have found that dengue virus-specific CD4+ and CD8+ cytotoxic T cells (CTL) are generated after primary dengue virus infections and that these CTL can produce cytokines such as interferon-(IFN-), interleukin-2 (IL-2), tumor necrosis factors and (TNF-, TNF-) in response to exposure to heterologous dengue viruses in vitro, and lyse dengue virus-infected autologous cells [Kurane et al., 1989, 1990; Mathew et al., 1996; Gagnon et al., 1999]. CD4+ T cells are classified as T-helper (Th) type 1 or 2, based on their ability to produce certain cytokines. Th1 cells produce IFN-, IL-2, and lymphotoxin, whereas Th2 cells produce IL-4, IL-5, IL-10, and IL-13 [O’Garra, 1998]. Plasma levels of IFN-are elevated in dengue infection and other markers of T-cell activation, such as soluble IL-2 receptors and soluble CD8, are higher in children with DHF than DF [Kurane et al., 1991; Green et al., 1999]. These findings have suggested a role for Th1-mediated immunopathology in the pathogenesis of DHF. IL-12 is a heterodimer of 70 kD (p70) and is made up of a p35 and a p40 chain [Trinchieri, 1995]. The p70 heterodimer is the active molecule. The p40 molecule alone is inactive but is inducible [Ma et al., 1995]. IL-12 has been shown to be a potent inducer of IFN-and enhances the cytotoxic activity of both natural killer (NK) and T cells [Trinchieri, 1994]. As IFN-levels have been found to be elevated in acute dengue [Kurane et al., 1991; Green et al., 1999], investigation of IL-12 production in DHF was warranted. Previous studies of DHF in children have found that levels of TNF-, soluble TNF receptors, and IFN-are elevated in DHF [Hober et al., 1993, 1996; Bethell et al., 1998; Green et al., 1999]. IL-10 has been found to be a potent inhibitor of proinflammatory cytokines, such as IL-12, IFN-, and TNF-[Trinchieri, 1995]. Therefore, the goal of this study was to investigate further the role of Th1 cytokines, such as IL-12, and that of counterregulatory Th2 cytokines, such as IL-10, to further elucidate the possible immunological mechanisms responsible for the development of the plasma leakage seen in DHF.