Epithelial chips of human foreskin or cervix infected in vitro with one strain of human papillomavirus type 11 (HPV-11) and subsequently transplanted to the renal capsule of athymic mice will yield, after 3 months of in vivo incubation, epithelial cysts that are morphologically transformed and appear identical in every way to human condylomata. These cysts synthesize virus RNA, DNA, proteins, and infectious virions. The cysts can be utilized as a source of virus for continued passage of infection. The original HPV-11 infecting material was a cell-free saline extract of pooled human vulvar condylomata. DNAs of other HPV types were not detected in this material by either dot blot or Southern blot analyses. The copy number of HPV-11 virus genomes per cell genome in experimental condylomata ranged from about 200 to 1,000, a range expected for episomal papillomavirus DNA. Analyses of cloned HPV-11 DNA (pBT-1) from experimental lesions demonstrated that the size and restriction endonuclease map of the HPV-11-Hershey isolate closely matched that of the prototype. A few nucleotide changes that were detected during analyses of pBT-1 DNA resulted either in no amino acid change or a conservative change of amino acid. Physical characterization of the cloned experimental HPV-11 DNA as well as HPV typing in clinical lesions and experimental cysts are presented.