Owing to its skin-sensitizing and fluorochromatic properties, fluorescein isothiocyanate (FITC) is employed frequently as an experimental hapten in mechanistic studies of contact allergy, particularly in the context of the role of migration and activation of Langerhans' cells. In this study we demonstrated that topical exposure of mice to FITC results in the selective development of activated lymph node cells (LNC) expressing a preferential type 2 cytokine-secretion profile, with high levels of interleukin (IL)-4 and IL-10, but low levels of interferon-gamma (IFN-gamma). Negative selection (complement depletion) identified CD4(+) T helper (Th)2-type cells as the primary source in activated LNC of the type 2 cytokines IL-4 and IL-10, whereas the low levels of IFN-gamma produced were derived exclusively from CD8(+) T cytotoxic (Tc) 1-type cells. A biphasic pattern of cutaneous inflammatory reactions was elicited by exposure to FITC, the early phase of which could be transferred passively with serum (presumably immunoglobulin E [IgE] antibody), whereas adoptive transfer experiments demonstrated that Th2-type CD4(+) cells were responsible for the delayed-type component of the dermal hypersensitivity reaction. In contrast with contact allergic reactions induced by other sensitizing haptens, which are considered to be largely Th1/Tc1-mediated immune processes regulated by Th2-type cells, these results suggest therefore that the skin lesions provoked in mice by FITC are primarily a result of the activation of Th2-type cells.