In a double-blind trial, 0.5% podofilox (podophyllotoxin) or placebo was applied by patients to their own genital warts in up to four treatment cycles. At some time during the study, 25 of the 56 podofilox treated patients and none of the 53 placebo group were completely wart-free. At the end of the treatment, 73.6% of the original warts in podofilox treated patients were gone compared with only 8.3% of those in the placebo group (mean percentage of total original wart area was reduced by 82.3% compared with 4.2%). 82% of the treated warts in the podofilox group and 13% in the placebo group had resolved at 6 weeks. Recurrence was observed in 34% of the previously resolved warts. Consistent with this rate of recurrence, new warts developed in a third of the subjects in each group at sites remote from the treatment site. There were no systemic adverse reactions, although transient inflammation, erosion, pain, and burning were common.