We report propagation of human papillomavirus (HPV) type 11 in human xenografts in the severe combined immunodeficiency (SCID) mouse and compare this new animal model for HPV infection to the previously established athymic nude mouse model. HPV-11-infected foreskin fragments grafted under the renal capsule of SCID mice formed large epithelial cysts that had the histologic and immunocytochemical features of HPV infection. This infection was successfully passaged to nude mice. Viral particles that reacted to an antibody directed to HPV-11 virions were identified from samples recovered from the SCID and nude mice. Viral DNA sequence analysis confirmed that the passaged virus was HPV-11. In a comparative experiment of the nude mouse and SCID mouse models, the latter produced HPV-11-infected xenografts that were larger and more often positive for HPV by immunocytochemistry and presence of viral mRNA than those propagated in the former model. Finally, we observed that growth of HPV-11-infected foreskin fragments in the SCID mouse model is not restricted to the kidney as in the nude mouse, but also can occur in the subcutis and the peritoneum.