We report 28 patients with advanced chronic graft-versus-host disease (cGVHD) treated with extracorporeal photopheresis (ECP). All had failed conventional immunosuppressive therapy. Of the patients, 27 had extensive cGVHD and 20 had more than 50% cutaneous surface area involvement. ECP was initiated approximately 2 years after onset of cGVHD and 3 years following allogeneic stem cell transplantation and administered fortnightly for 4 months and then monthly. Response was assessed using quantifiable disease measures, including skin score, liver function tests (LFTs), blood counts, and lung function tests. Regression analysis allowed assessment of any pretreatment clinical or laboratory parameters that predicted response. There were 25 patients who completed 3 months and 21 who completed 6 months of treatment. Systemic immunosuppression was stable or reduced in 86% of patients. There were 3 patients who died from cGVHD. After 6 months, median skin scores were 53% lower (P =.003) in sclerodermoid and lichenoid disease. Of 6 patients with mucosal ulceration, 3 improved. A nonsignificant improvement of LFTs occurred. We infer that ECP is effective even in patients with extensive cutaneous cGVHD of 2 years duration that is resistant to conventional therapy. Furthermore, both sclerodermoid and lichenoid subtypes responded. However, no baseline parameters predicted a favorable response to ECP, so patient selection must continue to be made on clinical grounds.