IL-12 deficiency has been shown to promote photocarcinogenesis in mice. As UVB-induced inflammation is an important tumor-promoting event in the development of skin tumors, we determined the effects of IL-12-deficiency on UVB-induced inflammatory responses in mice. For this purpose, IL-12-knockout (IL-12 KO) and their wild-type counterparts were subjected to a photocarcinogenesis protocol; skin and tumor samples were collected at the termination of the experiment, and analyzed for biomarkers of inflammation and their mediators. We found that the levels of infiltrating leukocytes, myeloperoxidase, proliferating cell-nuclear antigen (PCNA), COX-2, PGE2, and the proinflammatory cytokines IL-1beta, TNF-alpha, and IL-6 were higher in the UVB-exposed skin of IL-12 KO than in that of wild-type mice. In a short-term experiment, pretreatment of IL-12 KO mice with rIL-12 (50 ng per mouse) before each exposure to UVB increased the repair rate of UVB-induced cyclobutane pyrimidine dimers, while inhibiting UVB-induced increases in myeloperoxidase, COX-2, PGE2, PCNA, TNF-alpha, and IL-1beta in the skin as compared with non-rIL-12-treated IL-12 KO mice. Similarly, tumors of IL-12 KO mice expressed higher levels of inflammatory responses than those of wild-type mice. Together, our data suggest that IL-12 KO mice are more susceptible to both UVB-induced inflammation and photocarcinogenesis because of the deficiency in the repair of UVB-induced DNA damage.