There is an association between human papillomavirus (HPV), in particular types 16 and 18, and premalignant and malignant disease of the cervix. At present it is not possible to say that this is a causal association but in vitro transformation studies indicate that these viruses can transform primary mammalian cells in cooperation with Ha-ras. This may mean that these viruses have at least a c-myc like activity which is consistent with their ability on their own to immortalize primary keratinocytes. The fact that HPV6 can also transform mammalian cells, at a low frequency, in cooperation with Ha-ras indicates the need to use appropriate cells and systems that will elucidate differences in virus-cell interactions between benign HPV types 6 and 11 and the viruses associated with severe disease 16 and 18.