The successful use of phototherapy, especially psoralen plus UVA (PUVA) therapy, in the treatment of a variety of skin diseases is well known. Because the pathology of diseases such as vitiligo, alopecia and lichen planus is thought to involve immune mechanisms, the beneficial effect of PUVA may be due to immunosuppression. PUVA treatment can induce suppression in two ways. In the first (local suppression) psoralen is applied topically, the skin is irradiated with UVA and the contact allergen is applied directly to the irradiated skin. The induction of contact hypersensitivity (CHS) is suppressed and suppressor cells are found in the spleens of treated animals. Systemic suppression results from the injection of psoralen followed by exposure to UVA. The contact allergen is then applied at a distant non-irradiated site. CHS is suppressed and antigen-specific suppressor cells are found in the spleens of treated mice. The ability to induce specific immunosuppression may provide novel methods of inhibiting unwanted immune responses. We have demonstrated that graft rejection and the induction of graft-versus-host disease can be suppressed in an antigen-specific manner by UV radiation. Thus phototherapy may provide promising new treatments for suppressing graft rejection and perhaps may be beneficial in the treatment of autoimmune disease and allergic reactions