Maternal congenital transmission of infectious murine leukemia virus, primarily via milk, was the major route of virus spread in Lake Casitas (LC) wild mice and in crosses of LC mice with uninfected wild and laboratory mice. An indirect extrachromosomal male transmission in utero of LC virus also readily occurred in matings of viremic LC males with C57L females but apparently not with other uninfected wild or NIH Swiss females. Both amphotropic and ecotropic classes of LC murine leukemia viruses were potentially transmissible by congenital and venereal epigenetic means and could induce the same two diseases, lymphoma and paralysis, that occurred naturally in LC wild mice. Lymphoma and paralysis both failed to occur in uninfected LC mice or their hybrid progeny that escaped congenital infection.