The transformed phenotype is markedly affected by Interferon (IFN) long term treatment in HeLa and Siha cell lines. Two months of continuous exposure to 100 and 1000 International Units (IU)/ml of human recombinant alpha IFN causes a drastic reduction of anchorage independent growth in soft-agar. No effect on in vitro growing potential was observed at the same concentrations. This antiproliferative effect in soft-agar was more pronounced in Siha than in Hela cells and was concentration and time dependent. The Human Papillomavirus (HPV) sequences inserted in the cell genome apparently were unaffected as their RNA expression, indicating that IFN may modulate aspects of transformed phenotype regulated by genes other than HPV sequences.