Sixteen patients with lower genital intraepithelial neoplasia were treated by 5-fluorouracil (5-FU)/chemosurgery: colposcopically directed excision of neoplastic epithelium pretreated with topical 5-FU. 5-FU loosens the neoplastic epithelium, facilitating its removal from the underlying stroma in a safe, minimally traumatic fashion. 5-FU/chemosurgery was undertaken in patients with vaginal neoplasia or those with lower genital neoplasia who were immunosuppressed or had a neoplastic syndrome, because conventional methods are often difficult or inadequate for these problems. In all 16 patients, the neoplasia went into remission. Two immunosuppressed patients developed recurrences of lesser dysplasia when 5-FU maintenance therapy was interrupted because of pregnancy. It was found that 5-FU/chemosurgery, followed by monthly 5-FU maintenance, may be the best treatment for intraepithelial neoplasia of the vagina or lower genital intraepithelial neoplasia in patients who are immunosuppressed or have a neoplastic syndrome.