Mouse models are similar but not identical to human diseases. However, they are important for research into the pathogenesis underlying autoimmune diseases because they allow us to evaluate similarities and differences between human diseases and mouse models. In fact, experimental models and inbred lupus-prone mice are tools that enable a better understanding of the 'photosensitivity' or 'photocytotoxicity' phenomena in relation to autoimmunity. Genetic studies of MRL/lpr mice revealed that the appearance of macroscopic lupus erythematosus (LE)-like skin lesions needs the lpr mutation plus an additional factor in an autosomal dominant fashion. The candidate is ultraviolet (UV) B light, the susceptibility to which is regulated by the genetic background. Such a genetic background is also speculated to be important in human cutaneous LE patients. The translocation of anti-SS-A/Ro on cultured keratinocytes irradiated with UVB light is quantitatively different from photocytotoxicity, and the quantitative levels are significantly higher in systemic LE and subacute cutaneous LE than in discoid LE and normal controls. This review focuses on the lessons gleaned from mouse and human models, and discusses photosensitivity in human cutaneous LE.