Human papillomavirus (HPV) types 6 and 11 are usually found in benign genital lesions and laryngeal papillomas. However, the occasional occurrence of their DNAs in carcinomas of the genital tract and larynx suggests that they have some tumorigenic activity. In this paper, we have examined the cotransforming and transactivation activities of the E7 genes from these virus types and show that they cooperate with ras to transform primary cells, but at a greatly reduced level compared to HPV-16 E7. Although the efficiencies of transformation in vitro by HPV-6 and HPV-11 are low, it is striking that the cells that are transformed are highly tumorigenic in vivo in immunocompetent animals. Transactivation studies using the adenovirus E2 promoter demonstrated that both HPV-11 E7 and HPV-16 E7 could stimulate transcription to a similar degree. These results separate the transactivation and co-transforming activities of HPV E7 genes.