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Abstract A cytotoxic T lymphocyte (CTL) response to dengue virus-infected target cells is described. Effector cells were generated in an in vitro secondary culture and appeared to be T cells possessing both the Lyt 1.1 and Lyt 2.1 surface antigens. A stronger CTL response was noted with the H-2k haplotype compared to H-2d, and H-2 compatibility was required between CTL and target cells. CTL generated showed some cross-reactivity with target cells infected with Japanese encephalitis virus (JEV), another flavivirus, but not with target cells infected with an alphavirus, Sindbis. The significance and importance of these findings are discussed. Cytotoxic T lymphocytes (CTL) are activated following infection with a wide variety of viruses and may play both protective and pathogenic roles. Among the togaviridae, CTL has been demonstrated to the alphaviruses (9) but there is meagre evidence of a CTL response to flaviviruses. The dengue viruses (dengue 1-4) are flaviviruses and are the causative agents of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), an important cause of morbidity and mortality in many parts of the tropical world. Although the pathogenesis of DHF/DSS is not full