E6 (or E7) genes of some genital and cutaneous human papillomaviruses (HPVs) were compared for their ability to transform cells of a rat fibroblastic line (3Y1) by using recombinant retroviruses. The E6 gene of genital cancer-associated HPV 16 or 18 was found to induce a characteristic morphological change, i.e., densely packed arrays of elongated cells forming swirl patterns. This change is the same as that induced by the E6 gene of cutaneous cancer-associated HPV 5, 8, or 47, which we described previously. The E6 gene of HPV 1 or 11, associated with benign tumor of cutaneous or genital tissue, respectively, induced no such change. The E6 genes of all these cutaneous and genital HPVs enhanced anchorage-independent growth of the target cells induced by E7 gene of HPV 16 or 18, and this enhancing activity of HPVs 16, 18, and 47 was stronger than that of HPVs 1 and 11. A distinct type of morphological transformation of 3Y1 cells, i.e., rounded miniaturized cells that were densely packed without forming any distinctive arrays, was found to be induced strongly by E7 genes of HPVs 16 and 18, weakly by E7 of HPVs 1 and 11, and not at all by E7 of HPV 47. The results suggest that the intensity of the morphological change induced by E6 genes, rather than E7 genes, is correlated to the risk of malignant conversion of the lesion with which the corresponding HPVs are associated.