Ultraviolet (UV) light abrogates contact hypersensitivity (CHS) responses and induces hapten-specific tolerance. Because Th-1 cells are critically involved in CHS and are induced to develop by the cytokine interleukin (IL)-12, we asked whether IL-12 might overcome UV-induced local immunosuppression. C3H/HeN mice exposed to low doses of UV light over 4 d and hapten sensitized through the irradiated skin area with dinitrofluorobenzene showed profound inhibition of the CHS response, which was completely prevented upon intraperitoneal injection of murine recombinant IL-12 (rIL-12) after the last UV exposure. UV-treated mice resensitized 14 d after the first challenge displayed hapten-specific tolerance, whereas UV-exposed mice injected with rIL-12 before the first sensitization exhibited a vigorous CHS response. Furthermore, mice that were initially sensitized through UV-exposed skin also produced a significant CHS reaction when they received rIL-12 before resensitization. Adoptive transfer of spleen and lymph node cells from UV-irradiated mice treated with rIL-12 had no effect on the CHS response in recipient mice, whereas transfer of cells from UV-treated mice inhibited the immune response. These findings demonstrate that rIL-12 can prevent UV-induced local immunosuppression and overcome UV-induced hapten-specific tolerance.