Psoralen plus ultraviolet A irradiation (PUVA) has immunomodulatory effects and is used to treat a variety of immune-mediated dermatologic diseases. We administered PUVA to 103 patients for treatment of steroid-resistant acute graft-versus-host disease (GVHD) of the skin. Twenty-nine patients had related donors (12 HLA-mismatched) and 74 had unrelated donors (23 HLA-mismatched). The median onset of GVHD was day 13 after transplantation, and the median onset of PUVA treatment was day 46. PUVA was administered as secondary therapy for 86 patients and tertiary therapy or greater for 17 patients. The median number of treatments was 16, and the mean cumulative exposure was 41 J/cm2. PUVA was generally well tolerated with 8 patients discontinuing therapy because of toxicity. At the start of PUVA treatment, 48 patients had rash affecting >50% of their body surface area (BSA), and 91 had rash involving >25% BSA. Of 65 patients who were evaluated after 6 weeks of PUVA treatment, 11 still had rash involving >50% BSA, 24 had rash involving >25% BSA, and 24 had no rash. The mean daily dose of prednisone at the start of PUVA therapy was 1.6 mg/kg compared to 0.7 mg/kg after 6 weeks of therapy. Fifty-nine patients (57%) did not require additional therapy for skin GVHD after starting PUVA. Ninety-two percent of patients developed chronic GVHD. Fifty-three patients (51%) remain alive at 129-1883 days after transplantation. These results suggest that PUVA can be an effective therapy for steroid-resistant acute GVHD of the skin.