Photoimmunology evolved from experiments carried out in the 1970s on the immunology of cancer. In studying the antigenic properties of skin cancers induced in mice by UV radiation, I found that most of these tumors failed to grow when transplanted into normal, syngeneic mice but grew progressively in immunosuppressed mice. Thus, these UV-induced skin cancers were highly antigenic. The critical question was, how can these antigenic skin cancers escape immune rejection in their primary host? The answer was that exposing their skin to UV radiation prevented mice from triggering an immune response against their tumors. The failure to reject these tumors was owing to the development of UV tumor-specific regulatory T cells during the course of irradiation. In unraveling the mechanisms of this effect of UV, much has been learned about the immunology of the skin, including the function of Langerhans cells, the migration of immune cells in skin, the role of antigen-presenting cells in directing the immune response, and the role of keratinocytes as producers of immunological mediators. Thus, photoimmunology helped demonstrate that skin is an important immunological organ, and that the immune system can be influenced by the external environment via the skin.