Cytotoxic T lymphocytes (CTL) are an important protective mechanism in viral infection and can be effective against tumours. We have investigated the tumour-associated E6 and E7 genes of human papillomavirus type 16 as CTL targets. In H-2b mice we have defined epitopes in E6 and E7 which can readily generate CTL in vivo and we have shown that HLA-A2.1 transgenic mice can generate an HLA-A2.1-restricted response. We have been unable to reveal a primed CTL response in humans. These paradoxical findings imply that human papillomavirus may fail to stimulate a systemic CTL response and/or employ strategies for evading or down-regulating such a response.