Long-lasting and complete remission was obtained in a 48-year-old patient with refractory pemphigus vulgaris by an experimental treatment protocol that tries to synchronize plasmapheresis with subsequent pulse cyclophosphamide therapy. The rationale of the approach tries to utilize the plasmapheresis-induced increased proliferation of pathogenic cell clones for partial deletion of these clones through application of maximum pulse immunosuppression treatment during the period of assumed maximum proliferation and, thus, maximum vulnerability of the antibody-producing cells. The treatment schedule consisted of initial withdrawal of immunosuppressive drug therapy, repeated large-volume plasmaphereses substituted with immunoglobulin-free albumin solutions, subsequent application of high-dose (36 mg/kg of body weight) cyclophosphamide therapy, and low-dose maintenance immunosuppression for several months. As a result, our patient remained disease free over a follow-up period of 40 months without any further immunosuppressive treatment. Stimulation of postexchange antibody production and subsequent application of high-dose cytotoxic drugs might be a valuable tool in the management of refractory pemphigus vulgaris and, possibly, in the management of other autoantibody-mediated diseases.