A 74-year-old woman with vulvitis circumscripta plasmacellularis was successfully treated with intralesional injections of interferon alpha. Although the patient had been previously treated unsuccessfully for 5 years with topical administration of a potent corticosteroid, with cryotherapy, and with surgical procedures, the disease continually recurred. A course of interferon alpha resulted in a significant clinical improvement of the lesions, a histologically verified decrease of plasma cell infiltrate, and the disappearance of the antigen of herpes simplex virus that had been detected before treatment by direct immunofluorescence staining of the lesion. This clinical course demonstrates the effectiveness of local injections of interferon alpha into those lesions with vulvitis circumscripta plasmacellularis that did not previously respond to conventional therapy. Therefore an implication exists that herpes simplex virus infection may be one of the factors involved in the pathogenesis of this disease.