It is almost three decades ago that it was discovered that ultraviolet radiation (UV) can compromise the immune system. UV suppresses immune responses in several ways. It inhibits the function of antigen-presenting cells, induces T cells with suppressor activity and induces the release of immunosuppressive cytokines. The latter phenomenon is mainly responsible for systemic immunosuppression. Although UV can also target cytoplasmic and cell membrane components, UV-induced DNA damage has been recognized as the most important molecular structure in mediating UV-induced immunosuppression. Recently, it was observed that interleukin-12 (IL-12), which antagonizes UV-induced immunosuppression, can accelerate the removal of UV-induced DNA lesions, probably via inducing DNA repair. Hence, it is tempting to speculate that the activity of IL-12 to reduce UV-induced immunosuppression may be due at least partially to this new biological activity of IL-12.