We conducted a randomized, double-blind, placebo-controlled trial of two forms of topical interferon therapy for condyloma acuminata in women. Gel containing 10(6) IU of leukocyte interferon/g, with or without nonoxynol-9, was compared with treatment with gel base alone. Eighty-nine patients applied the gel three times a day for four weeks and were studied for at least 16 w. Side effects were generally mild and limited to the site of application for all three drugs. Although a transient, statistically significant therapeutic effect was noted early in the course of treatment with both interferon gels as compared with placebo, this effect was lost by the end of the follow-up period, possibly because of a generally high response rate in patients receiving placebo. Hence, there was no overall difference in the number of patients with a partial or complete response to any of the agents by the end of therapy or by the end of the study.