Twenty nonpregnant women with condylomata acuminata of the vagina were studied to assess the effectiveness of weekly topical 5-fluorouracil application. All patients were instructed to insert an applicator one-third full of 5% 5-fluorouracil cream (approximately 1.5 g) deeply into the vagina at bedtime once each week for ten consecutive weeks. The response to this treatment was evaluated by colposcopy and cytology three and six months after initiation of therapy. Seventeen patients (85%) showed no evidence of the disease when examined three months after treatment. Three women, although improved, had persistent vaginal condylomata, which responded to a second course of 5-fluorouracil given twice each week. After a follow-up of ten to 20 months (mean 15.8 months), 16 patients remained free of disease, two developed recurrence, and two were lost to follow-up. Two women developed mild vulvar irritation and eight had vaginal discharge. It is concluded that weekly topical application of 5% 5-fluorouracil is well tolerated and highly effective in treating vaginal condylomata acuminata.