Reduced immunity following exposure of skin to UV radiation (UVR) may explain the positive latitude gradient measured for a number of autoimmune diseases (greater incidence of disease with residence at higher latitudes), including multiple sclerosis, allergic asthma and diabetes. Humans obtain> 80% of their vitamin D 3 by exposure of skin to UVR in sunlight. In experimental models, both vitamin D 3-dependent and vitamin D 3-independent pathways have been implicated in the mechanisms of UVR-induced systemic suppression of immunity. However, where does the balance of control lie? How important is vitamin D 3 other than providing a biomarker of sun exposure? Are other molecules/pathways activated by UVR more important? Murine and human studies suggest many molecules may play a role and their participation may vary with different diseases and the time of UVR exposure or vitamin D 3 sufficiency/deficiency. Although low vitamin D 3 levels have been associated with increased prevalence and progression of human autoimmune diseases, the benefits of supplementation with vitamin D 3 have not been definitive. Vitamin D 3 levels are a measure of past sun exposure but vitamin D 3-dependent and vitamin D 3-independent immunosuppressive effects of UVR may play a role in control of autoimmune diseases.