Interleukin 6 (IL-6), a multi-functional cytokine, is expressed constitutively by epidermal Langerhans cells and can be produced also by keratinocytes following stimulation. We have investigated the production of cutaneous IL-6 following topical exposure of mice to oxazolone, a potent contact allergen. Homogenates of ear skin prepared from untreated BALB/c strain mice, or from mice exposed on the dorsum of both ears to vehicle alone, contained low levels of IL-6. Topical application of oxazolone to the ears of mice induced a rapid and dose-dependent increase in IL-6 expression that was maximal 4-8 h following application and remained elevated for up to 24 h. Under the same conditions of exposure the expression of a second epidermal cytokine, interleukin 10, a product of keratinocytes, was unaffected. It is concluded that topical exposure to the chemical allergen oxazolone results in the selective stimulation of cutaneous cytokine production. The experimental approach described herein provides a simple and reliable method for the investigation of induced changes in the expression of skin cytokines.