The role of CD4+ vs CD8+ T cells in contact hypersensitivity (CHS) remains controversial. In this study, we used gene knockout (KO) mice deficient in CD4+ or CD8+ T cells to directly address this issue. Mice lacking either CD4+ or CD8+ T cells demonstrated depressed CHS responses to dinitrofluorobenzene and oxazolone compared with wild-type C57BL/6 mice. The depression of CHS was more significant in CD8 KO mice than in CD4 KO mice. Furthermore, in vivo depletion of either CD8+ T cells from CD4 KO mice or CD4+ T cells from CD8 KO mice virtually abolished CHS responses. Lymph node cells (LNCs) from hapten-sensitized CD4 and CD8 KO mice showed a decreased capacity for transferring CHS. In vitro depletion of either CD4+ T cells from CD8 KO LNCs or CD8+ T cells from CD4 KO LNCs resulted in a complete loss of CHS transfer. LNCs from CD4 and CD8 KO mice produced significant amounts of IFN-γ, indicating that both CD4+ and CD8+ T cells are able to secrete IFN-γ. LNCs from CD8, but not CD4, KO mice were able to produce IL-4 and IL-10, suggesting that IL-4 and IL-10 are mainly derived from CD4+ T cells. Intracellular cytokine staining of LNCs confirmed that IFN-γ-positive cells consisted of CD4+(Th1) and CD8+(type 1 cytotoxic T) T cells, whereas IL-10-positive cells were exclusively CD4+(Th2) T cells. Collectively, these results suggest that both CD4+ Th1 and CD8+ type 1 cytotoxic T cells are crucial effector cells in CHS responses to dinitrofluorobenzene and oxazolone in C57BL/6 mice.