This study investigated systemic and local cell mediated immunity to HPV in patients with cutaneous warts in order to understand the basis for their persistence or regression. The aim of the first part of the project was to examine HPV-specific lymphoproliferative responses from the peripheral blood of patients with cutaneous HPV infection. Proliferative T cell responses towards purified HPV in vitro were demonstrated in some individuals but frequently responses were weak or non existent. Patients whose warts were regressing (or had fully resolved) did not show increased lymphoproliferative responses towards purified HPV in vitro compared with patients whose warts showed no change. HPV-specific T cell clones were not obtained either directly from peripheral blood mononuclear cells stimulated with purified HPV, or after expansion of these cells with anti-CD3 and anti-CD28 antibodies. Any HPV-specific modulation of immunity may be more apparent locally in the lesion, than in systemic circulation. Therefore three studies were conducted in order to investigate local immunity in cutaneous warts. In the first, an immunohistochemical approach was taken. The density of Langerhans' cells was reduced in the epidermis of warts compared with normal skin. Epidermal keratinocytes did not express intercellular adhesion molecule-1 (ICAM-1) in cutaneous warts, but the vascular expression of ICAM-1 and E-selectin was increased in the dermis of warts compared with normal skin. This may account in part for the observed increase in numbers of T cells in the dermis of warts compared with normal skin. However, few T cells were found in the epidermis of warts, compared with an inflammatory skin disease such as psoriasis.