A randomized, double-blind, placebo-controlled trial was conducted to assess interferon-beta efficacy and safety in the treatment of anogenital condylomatous lesions. One hundred patients received a daily intramuscular injection of either interferon-beta (IFN-beta) (2 MIU/day) or placebo for 10 days. Of 94 evaluable patients, the complete response rate observed 8 weeks after treatment was significantly higher in the group receiving IFN-beta, as compared to the placebo-treated group (51% vs 28.9%, P < 0.05). After one year, 24 patients (100%) out of 24 complete responders to IFN-beta who attended for follow-up remained free of lesions. Twelve of 13 patients with complete response to placebo (92.3%) remained free of lesions after one year. Side effects were mild and no significant analytical changes were observed. In conclusion, interferon-beta is an effective and safe treatment for long-term eradication of anogenital condylomatous lesions.