Treatment of genital warts is problematic. Numerous treatment modalities are available, but response to any therapy often is unsatisfactory. Recently, studies have suggested that interferons would be effective in the treatment of some genital warts. To compare carbon dioxide laser with or without adjuvant subcutaneously administered interferon alpha-2b in the treatment of genital human papillomavirus infection. One hundred randomized women with genital HPV infection were treated with carbon dioxide laser and adjuvant systemic interferon alpha-2b or carbon dioxide laser and placebo. Patients were followed colposcopically, cytologically, and by HPV DNA testing for 6 months. Complete response was seen in 62% patients who received adjuvant interferon, and in 68% patients who received placebo. However, recurrence was less common in patients treated with interferon who were infected with HPV 16/18. Only a subgroup of patients, women infected with HPV DNA 16/18, benefited from adjuvant systemic interferon treatment.