Molecularly cloned DNA of papilloma virus and murine retrovirus genomes have been used to define the structural and functional organization of these viruses. An in vitro focus assay for bovine papilloma virus and its viral DNA has been developed for two mouse cell lines. Using this assay, a molecularly cloned 69% viral DNA fragment has been found which induced tumorigenic transformation of these cells. Using a similar DNA infectivity assay, the transforming (and p21 src coding region) of Harvey murine sarcoma virus (Ha-MuSV) has been localized to a 1.3 kbp segment in the left half of the viral genome. The viral terminal repeat sequence is important for "rescue" of Ha-MuSV by helper-independent murine leukemia virus (MuLV). The leukemogenic activity of Friend-MuLV has been localized to the right half of the linear viral DNA. The physical maps of several endogenous MuLV DNAs have been derived. They indicate that a wild Asian mouse and many inbred mice contain a highly related ecotropic MuLV. An ecotropic-specific DNA probe has been derived for env gene sequences. This probe has been used to show that endogenous ecotropic MuLV DNAs in normal mouse cells are composed of a virtually complete copy of the viral genome.