Warts are squamous epithelial tumors induced by PAPOVA viruses present in vertebrates. Human warts are induced by the homonymous papillomaviruses (HPVs). These DNA viruses have a characteristic electron microscopic appearance, and their structure is well known, but they cannot be cultivated in vitro. Although warts are mainly benign, they may turn into premalignant or malignant lesions. Conversely, the origin of nonmelanocytic skin and mucous membrane tumors may be related to the presence of HPV. The study of Shope papillomavirus naturally occurring in warts of western cottontail rabbits provides interesting information to understand papilloma virus (PV)/epithelial interaction (Table 1).1 (1) PV may induce benign tumors in the skin. The rate of induction depends on the magnitude of the inoculum, species inoculated, and individual factors. (2) Experimentally induced epidermal hyperplasia increases susceptibility to infection. (3) Tumors may persist and spread or regress (animals in which tumors disappear are called regressors). Papillomas may remain benign or convert to metastasizing carcinomas. (4) Regression may affect all warts or be partial or transitory. (5) Infection and regression are related to host immune response. The latter has been better studied vis-a-vis viral protein and nucleic components and is humoral and cellular. (6) Malignant tumors are notoriously poor in infective virions but may harbor viral DNA. (7) Regressor animals are resistant to reinfection but not absolutely so. (8) Regressing lesions frequently show inflammatory features similar to those of graft rejection. (9) Regression is hampered by immunosuppresants.