In this study, we observed that mice lacking the IL-1 receptor (IL-1R) (IL1r^-/-) or deficient in IL1-β developed multiple epidermal cysts after chronic UVB exposure. Cysts that developed in IL1r^-/- mice were characterized by the presence of the hair follicle marker Sox 9, keratins 10 and 14, and normal melanocyte distribution and retinoid X receptor-α expression. The increased incidence of cysts in IL1r^-/- mice was associated with less skin inflammation as characterized by decreased recruitment of macrophages, and their skin also maintained epidermal barrier function compared with wild-type mice. Transcriptional analysis of the skin of IL1r^-/- mice after UVB exposure showed decreased gene expression of proinflammatory cytokines such as tumor necrosis factor-α and IL-6. In vitro, primary keratinocytes derived from IL1r^-/- mice were more resistant to UVB-triggered cell death compared with wild-type cells, and tumor necrosis factor-α release was completely blocked in the absence of IL-1R. These observations illustrate an unexpected yet prominent phenotype associated with the lack of IL-1R signaling in mice and support further investigation into the role of IL-1 ligands in epidermal repair and innate immune response after damaging UVB exposure.