Twelve patients with vaginal intraepithelial neoplasia received topical therapy with 5% 5-fluorouracil cream. Six patients had carcinoma in situ, 5 had moderate dysplasia, and 1 had mild dysplasia. Five patients responded to 1 treatment course. Six patients required 2, and 1 patient required 3 courses of therapy to respond. Three patients developed recurrent vaginal intraepithelial neoplasia 11–16 months after therapy and were retreated with topical 5-fluorouracil. Vaginal irritation occurred in all patients but was limited to the duration of the treatment course.