Photopheresis is a relatively safe and technically simple modality for immunomodulation. The extracorporeal activation of a drug with UVA constitutes a novel form of drug delivery. The usefulness of this system in erythrodermic CTCL is well established. Immunomodulating therapy can thus be conducted outside the host, where controlled conditions permit cellular manipulations not possible in the intact patient. This system is an excellent paradigm for future immunomodulating therapies in diseases such as pemphigus vulgaris and lupus erythematosus.