Infection by human papillomavirus type 16 (HPV16) has been associated with cervical dysplasia and carcinoma. To detect a possible cellular immune response against HPV16, we investigated the induction of T cells specific for antigens encoded by the virus. Two CD4+ T-cell lines with a specific proliferative response were isolated from the spleens of rats vaccinated using vaccinia virus vectors expressing E6 or E7 and challenged with syngeneic HPV-transformed cells. Two CD8+ T-cell lines with a specific cytotoxic activity were obtained from mice immunized using a syngeneic squamous cell tumour cell line transfected with the full-length HPV16 DNA. These results demonstrate that both CD8-mediated cytotoxic responses and CD4-mediated delayed-type hypersensitivity responses are involved in immunologic reactions to HPV antigens.