Alpha interferon did not prevent the persistence or expression of human papillomavirus (HPV) types 6 or 11 in respiratory tract papillomas. Seventeen patients receiving interferon therapy for a minimum of six months and a maximum of 39 months still had one to ten copies per cell genome of HPV DNA in their laryngeal tissues, seen by Southern blot hybridization. In papillomas that recurred during treatment, HPV RNA could be detected by in situ hybridization, and capsid protein could be detected by immunoperoxidase staining. Persistence of the HPV DNA, and recurrences that occurred during therapy, are attributed to the failure of interferon therapy to eliminate latent virus.