The effectiveness of intraurethral 5-fluorouracil and systemic administration of interferon-alpha 2a in the therapy of condylomata acuminata or flat condylomata of the urethra is assessed. From March 1986 to September 1991, 1,372 male sexual partners of women with condylomata acuminata, flat condylomata or cervical intraepithelial neoplasia underwent urethroscopy and brush cytological examination of the urethra. Of these men 305 (22.23%) had intraepithelial human papillomavirus (confirmed cytologically) and 284 were treated. The best treatment modalities, regardless of the type of lesion, were the combinations of 5-fluorouracil plus high (95.34%) and low (70.58%) dose interferon-alpha 2a. Interferon-alpha 2a can be used as first line treatment with 5-fluorouracil cream in patients with intraurethral condylomata acuminata or flat condylomata.