Two hundred three patients (median age 26 years; range 18-45) with untreated multiple and widespread anogenital condyloma were randomly assigned to one of four study arms in order to compare the efficacy, toxicity, and tolerability of recombinant interferon alpha-2b with those of diathermocoagulation. Of 200 evaluable patients, 51 were treated intramuscularly (IM) with 3 x 10(6) U (3 MU)/m2 daily for 3 weeks (total dose 63 MU/m2), 50 received subcutaneous thrice-weekly injections of 3 MU/m2 for 4 weeks (total dose 36 MU/m2), 51 underwent diathermocoagulation, and 48 were not treated and were used as a control group. Six months after the end of treatment, the overall response rate (complete and partial responses) was 70%: 57 and 82% for patients receiving interferon alpha-2b (IM and subcutaneously) and diathermocoagulation, respectively, and 8% for the control group. After 6 months from therapy, no significant differences in complete response were found among the different types of treatment: 20, 20, and 35% for the two interferon groups and the diathermocoagulation group, respectively. Fifteen and two complete responders in the cauterization and interferon groups, respectively, experienced disease recurrence (P less than .01). All patients given interferon therapy complained of flu-like symptoms, which declined progressively after the first week of treatment. Fatigue, lasting as long as patients received interferon, was the most prevalent chronic side effect. We conclude that systemic recombinant interferon alpha-2b is active in treating patients with primary condyloma lesions and does so as well as cauterization.(ABSTRACT TRUNCATED AT 250 WORDS)