Seventy nonpregnant women with extensive condylomata of the vagina were treated either with intravaginal 5-fluorouracil (5-FU) cream or the CO2 laser. Treatment results were correlated with the morphologic type of condylomata, ie, papillary acuminata (58 patients), and flat condylomata (12 patients). Ten and 31% of women with Condylomata acuminata had persistent disease within nine months after a single course of 5-FU and laser therapy, respectively. Total failure rates after a second either 5-FU or laser treatment were 3.4%. The failure rates for flat condylomata were 50 and 16.6% after 5-FU and laser treatment, respectively. Recurrences, defined as the development of new disease after a nine-month disease-free period were 7.4 and 10% for C acuminata after 5-FU and laser therapy, respectively. Twenty-five and 20% of women with flat condylomata treated respectively with 5-FU and the laser had recurrent disease. Acute urethrovulvar vaginitis occurred in 12.2% of the 5-FU-treated group, whereas complications were absent in those treated with the laser. Although the number of patients in each treatment arm was small and the patients were not randomized, intravaginal 5-FU therapy with protection of the vulva seems more cost effective for C acuminata in nonpregnant women than the laser, which requires general anesthesia. Flat condylomata are best managed by laser therapy. Refractory lesions successfully respond to laser-5-FU combination therapy.