Ultraviolet (UV) radiation, in particular the midwavelength range (UVB; 290-320 nm), is one of the most significant risk factors for the development of nonmelanoma skin cancer. UVB radiation-induced immunosuppression, which occurs in both humans and laboratory animals, contributes to their pathogenesis. However, there are conflicting reports on the relative role of CD4+ and CD8+ T cells in UVB induced skin cancer. The purpose of this study was to delineate the contribution of these two cell subpopulations to UVB induced immunosuppression and tumor development using C3H/HeN (WT), CD4 knockout (CD4-/-) and CD8 knockout (CD8-/-) mice. We observed that UVB induced skin carcinogenesis was retarded in terms of number of tumors per group, tumor volume and percentage of mice with tumors, in mice deficient in CD4+ T cells compared with wild-type mice, whereas significantly greater (P < 0.05) numbers of tumors occurred in CD8-/- mice. These results indicate that, CD4+ T cells promote tumor development while CD8+ T cells have the opposite effect. Further, we found that CD4+ T cells from tumor-bearing mice produced interleukin (IL)-4, IL-10, and IL-17 whereas CD8+ T cells produced interferon-γ. Manipulation of T-cell subpopulations that are induced by UVB radiation could be a means of preventing skin cancers caused by this agent. © 2010 The American Society of Photobiology.