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The papillomaviruses, which are widely distributed in nature, typically induce benign skin tumours (warts) in their natural hosts (reviewed in ref. 1). These viruses are members of the papovavirus group, as are the polyomaviruses2. In contrast to polyomaviruses such as SV40, polyoma and BK (reviewed in ref. 3), the papillomaviruses have not been extensively studied, primarily because of the lack of a suitable tissue culture system. In general, the proliferative skin changes induced by the papillomaviruses are limited to the epidermal cells, and the viruses have a very narrow host range. However, some bovine papilloma viruses (BPV) are exceptional in that they induce fibropapillomas in their natural host (cows); these BPV can also induce cellular transformation in tissue culture4–6 and fibroblastic tumours in heterologous animals, including hamsters7, mice5 and horses8,9. BPV DNA from virions can also transform rodent cells and is tumorigenic in hamsters10. Recently, a tissue culture focus assay11 in mouse cells (NIH 3T3 and C127) has been described for those BPV which are the aetiological agents of fibropapillomas in cows. The virally transformed cells, which did not contain infectious virus, grew in soft agar and were tumorigenic in nude (nu/nu) mice. We12 have recently molecularly cloned the entire genomes of BPV-1 and BPV-2 (ref. 13) in Escherichia coli K12 using the certified plasmid vector pBR322 (ref. 14). We now demonstrate that these cloned DNAs can transform NIH 3T3 and C127 cells. Further, a molecularly cloned fragment which contains 69% of the BPV-1 genome can also induce cellular transformation.