An earlier study by this group failed to demonstrate significant therapeutic effect of 4 weeks of systemic recombinant interferon (IFN)-alpha 2 monotherapy on anogenital condylomata acuminatum. The present study was undertaken to determine if 3 MIU of IFN given three times weekly for 4 consecutive weeks and starting immediately after CO2 laser ablation of all visible warts would be effective. In a multicenter placebo-controlled randomized double-blinded study of 130 evaluatable patients followed for 36 weeks after treatment, no beneficial effects were noted in terms of complete response (24 placebo vs. 23 IFN patients) and recurrences (38 placebo vs. 46 IFN patients). None of the pretreatment and demographic characteristics affected outcome with statistically significant differences. CO2 laser ablation combined with systemic recombinant IFN-alpha 2 was ineffective in this study as treatment of anogenital condylomata.