Background: The exposure of human skin to leaves and branches of litre (Lithraea caustica), a Chilean endemic tree, induces a severe contact dermatitis characterized by swelling and pruritus in susceptible individuals. The allergenic priniciple of litre is 3–pentadecyl (10–enyl) catechol (litreol), which is structurally similar to the allergens isolated from poison oak and poison ivy. All of them belong to a family of compounds named urushiols. As a proelectrophilic allergen, litreol must be intracellularly activated before modifying proteins of individuals exposed to it. As a result, self–peptides derived from litreol–modified intracellular proteins would be presented in the context of class I MHC molecules. We hypothesized that CD8+ T lymphocytes would play a major role during the effector phase of the immune response induced by those modified peptides. In order to test this hypothesis, we investigated the cellular immune response to litreol in Balb/cJ mice. The role of the different lymphocyte subpopulations in this response was assessed by immunodepleting mice of CD4+ or CD8+ T lymphocytes using specific monoclonal antibodies (mAbs). We report the observation that the contact dermatitis induced by litreol has two components: a primary response which does not require TCRαβ+ T cells, and a secondary response mediated mainly by CD8+ T cells and regulated by CD4+ T cells. Our results show that CD8+ lymphocytes play a central role as effectors of the secondary response to litreol. Furthermore, our data suggest that two functionally different CD4+ T subpopulations serve as regulators of the CD8+ T cell function: a CD4+ T helper population sensitive to a low dose of the depleting mAb, and CD4+ T suppressor population which is eliminated only with a high dose of depleting mAb.