Immunological unresponsiveness can be initiated by exposure of mice to UV radiation, followed by the introduction of certain antigens. These antigens include epicutaneously applied chemicals that induce contact hypersensitivity (CHS), and antigens that occur on skin cancers induced by UV radiation. Mice exposed repeatedly to high doses of UV radiation during UV carcinogenesis develop immunological unresponsiveness to UV radiation-induced skin cancers, which are highly antigenic. This unresponsiveness is associated with the appearance of suppressor T lymphocytes that are specific for tumors induced by UV radiation, even though these tumors express individually specific transplantation rejection antigens. Thus, the occurrence of suppressor cells with specificity for a set of non-cross-reacting tumors suggests that a common, UV-associated regulatory antigen or determinant may be present on UV-induced skin cancers. Suppression of CHS in mice by UV radiation can be induced by two different procedures. One involves applying the sensitizer directly on skin exposed to low doses of UV-B radiation and is thought to result from a direct effect of UV radiation on cutaneous Langerhans cells. The second involves application of the sensitizer to the unirradiated skin of mice or guinea pigs exposed several days earlier to a higher dose of UV-B radiation. The mechanism of the latter phenomenon is not well understood, but there is evidence that it results from an alteration of antigen presentation by splenic macrophages. Both forms of suppression are associated with the appearance of antigen-specific suppressor lymphocytes in the animals' spleens, which prevent the induction of CHS upon transfer to a normal recipient. Either or both of these pathways could be responsible for the formation of the suppressor cells involved in UV carcinogenesis. Recent studies suggest that UV radiation may also affect immunological responsiveness in humans as well as in animals. However, the extent of such alterations and the mechanisms by which they occur are still unknown.