Human papillomaviruses (HPVs) express various proteins which have been proven to interact with some cellular functions playing a role in cell cycle progression and differentiation. Therefore, these viral gene products might be candidates for interfering with IFN-mediated antiproliferative actions. Condyloma biopsies from patients subsequently demonstrated to be responsive or non-responsive to IFN treatment were investigated. mRNA levels of HPV genes and IFN-responsive genes were determined by RT-PCR and correlated with IFN responsiveness. Patients clinically nonresponsive to IFN demonstrated a characteristic HPV transcriptional activity differing from responder patients. Nonresponders expressed mostly early E7 mRNAs; responders demonstrated higher expression of the late L1 gene. This differential transcription of infecting HPV also correlated with the extent of IFN mediated antiproliferative effect. A hypothesis for further study is that HPV E7 may inhibit IFN responsiveness, while HPV L1 may promote IFN responsiveness.