Human papillomavirus type 11-Hershey (HPV-11-H) from an extract of genital warts has been serially passaged by infecting human foreskin chips that are then implanted in athymic mice (1. W. Kreider, M. K. Howett, A. E. Leure-Dupree, R. J. Zaino, and J. A. Weber (1987), J. Virol. 61, 590). Subsequent attempts to propagate HPVs present in other human lesions have not been successful. In an effort to identify the basis for the seemingly unique ability of HPV-11-H to propagate in the xenografts, we carried out extensive physical and functional characterizations of the cloned DNA, including restriction digestions, DNA sequencing of transcriptional control regions, and E2 trans-activation of the upstream regulatory region. We uncovered no significant differences compared to the prototype HPV-11 (K. Dartmann, E. Schwarz, L. Gissmann, and H. zur Hausen (1986) Virology 151,124; H. Hirochika, T. R. Broker, and L. T. Chow (1987) J. Virol. 61, 2599). Moreover, viral enhancer assays indicated that the observed stimulatory effect of pregnancy on condylomata and of estradiol on experimental cysts is likely an indirect one and could not be attributed to up-regulation of the HPV-11 transcriptional enhancer. © 1989.