Interleukin-10 (IL-10) is known to play a major role in suppressing immune and inflammatory responses by inhibiting the production of proinflammatory cytokines. Therefore, we hypothesized that IL-10 might be capable of suppressing allergic contact hypersensitivity. BALB/c mice were sensitized on the dorsal skin with dinitrofluorobenzene and challenged on the ears 6 d later. The effect of IL-10 on the elicitation phase of contact sensitization was determined by its intradermal injection into the pinnae of the mice at doses of 0.1-100 ng. At 24 and 48 h after challenge, ear swelling was suppressed in a dose-dependent manner by injection of IL-10 at doses of 10-100 ng. Maximal inhibition of ear swelling (46.9%) was observed after injection of 100 ng of IL-10. IL-10-injected ear skins showed less inflammatory cell infiltration and decreased edema at the dermis compared with controls. Because IL-10 is known to inhibit Th1 cytokines such as interferon-gamma, we examined whether the suppressive effect of IL-10 on ear swelling was accompanied by IL-10-induced inhibition of interferon-gamma. We found that IL-10 application suppressed interferon-gamma mRNA upregulation in challenged skin. Our results suggest that IL-10 significantly modifies the elicitation of allergic contact sensitivity reactions.