Contact hypersensitivity (CHS) is a T cell-mediated, Ag-specific skin inflammation induced by skin exposure to haptens in sensitized individuals. Th1/T cytotoxic 1 cells are effector cells of CHS, whereas Th2/T regulatory CD4+ T cells have down-regulating properties. We have previously shown that CHS to 2, 4-dinitrofluorobenzene is mediated by specific CD8+ effector cells, whose cytolytic activity is mandatory for induction of skin inflammation. In this study, using immunohistochemistry and RT-PCR analysis, we show that CD8+ T cells are rapidly recruited into the skin at the site of hapten challenge before the onset of clinical and histological signs of skin inflammation. This early CD8+ T cell recruitment is concomitant with: 1) transient IFN-γ mRNA expression suggesting local activation of effector cells; and 2) induction of keratinocyte (KC) apoptosis which gradually increased to a maximum at the peak of the CHS response. Alternatively, skin infiltration of CD4+ T cells occurred later and coincided with the peak of the CHS reaction and the beginning of the resolution of skin inflammation. Mice deficient in CD8+ T cells did not develop CHS, whereas mice deficient in CD4+ T cells developed an enhanced inflammatory response with increased numbers of CD8+ T cells recruited in the skin associated with massive KC apoptosis. These data show that CHS is due to the early and selective recruitment in the skin of CD8+ T cytotoxic 1 effector cells responsible for KC apoptosis.