Guinea pigs immunized with polypeptides derived from plantar and hand wart viruses developed both humoral and cell mediated immunity. The specificity of the antiserum was determined by indirect immunofluorescence (IF) tests and cellular immunity by intradermal tests. While whole plantar and hand wart virus particles (PV and HV) appeared to be immunologically analogous, they had different polypeptide patterns as shown by analysis on acrylamide slab gels. In particular, the P2 polypeptide (major virus protein) with different mol. wt. for PV (56750) and HV (54500) induced the production of high antibody titres in the animals and the immune sera specifically labelled wart substrates as shown in thie IF test, demonstrating that no cross humoral reaction occurs between these two polypeptides. Furthermore, a delayed hypersensitivity reaction was observed in P2 polypeptide-inoculated guinea pigs when whole particles were introduced in skin tests, but a total cross reactivity between PV and HV was noticed at the cellular level. However, the study of the virus isolated from the lesions of a patient (Ri) bearing extensive common hand warts has shown that the virus particles possessed all the biochemical and immunological characteristics of PV, in particular with regard to the P2 polypeptide. Such a case may represent plantar-like warts located on the hands.