Anogenital warts are a common clinical manifestation of genital infection with human papillomavirus type 6b (HPV-6b). Accumulating data indicate that an effective cellular immune response is required for the control of HPV infections. However, in a minority of patients there is a high rate of recurrence of wart lesions. We report the characterization of both local and systemic HPV-specific cellular immune responses in three patients with a history of recurrent genital warts. Although the patients had chronic recurrent wart lesions, we have shown that each had both detectable intralesional and peripheral HPV-specific T lymphocytes. Interestingly, the lesion-infiltrating T cells were specific for only one HPV antigen, focusing on only a few epitopes. Conversely, the T cells derived from peripheral blood recognized a broader range of HPV antigens. The characteristics of the HPV-specific cellular immunity that we have shown in these patients may be indicative of a failure to mount an effective response against the virus. This would be consistent with the chronic nature of the disease in these specific individuals. These observations could be relevant to the design and immunomonitoring of immunotherapeutic vaccines for persistent HPV infections.