Contact hypersensitivity (CHS) induced by a hapten is thought to be mediated by T helper type 1 (Th1) cells. However, FITC can induce contact allergy in vivo, and in vitro studies suggest that this response is Th2‐type driven. We compared CHS reactions induced by FITC or dinitrofluorobenzene (DNFB), a well‐known Th1 inducing hapten, in Balb/c mice, C57/B6 mice, and several gene knock‐out mice, and investigated the role of Th1/Th2 cytokines, T cell populations, eosinophils, and mast cells. Balb/c mice (Th2 dominant strain) had a stronger response to FITC than C57/B6 mice (Th1 dominant strain). The skin inflammation was characterized by edema and eosinophilia, and serum IgE levels were elevated following FITC challenge. All responses were enhanced by a second round of sensitization. Anti‐TNF‐α or anti‐very late antigen‐4 (VLA‐4) antibody partly inhibited both FITC‐ and DNFB‐induced CHS. Pretreatment of mice with anti‐IL‐4 antibody, anti‐IL‐5 antibody, recombinant INF‐γ, or the mast‐cell depleting agent 48/80 significantly diminished edema formation, and Stat6^–/– mice were fully protected from FITC‐induced CHS, while DNFB‐induced CHS was enhanced (Stat6^–/–, mast cell depletion) or not affected (anti‐IL‐5 antibody). Further, mice lacking CD4⁺ T cells and mice lacking both CD8 and MHC II showed very little reaction at all to FITC, while the absence of CD8 T cells alone or MHC II alone conferred partial protection only. These findings indicate a contribution of MHC II‐independent CD4⁺ T cells and/or CD4⁺ NKT cells to the Th2 response triggered by FITC in vivo, and makes FITC‐induced CHS a suitable animal model for atopic dermatitis.