We have studied the effect of IFN on the transcription of integrated HPV 18 DNA in HeLa cells. We found that the amount of cytoplasmic HPV 18 mRNA was markedly reduced in HeLa cells treated with 10(3) IU/ml of IFN alpha or gamma, and that the inhibitory effect was dose dependent and was detectable by 12h after the addition of IFN. Furthermore, northern blot analysis indicated that IFN remarkably reduced 3.4 kb mRNA species of HPV 18 transcripts in HeLa cells. In contrast, the level of beta-actin mRNA was found to increase in IFN treated cells. The results suggest that IFN alpha and gamma selectively inhibited HPV 18 gene expression at the level of transcription.