Aging wild mice (Mus musculus domesticus) from several different trapping areas in southern California are uniquely prone to a naturally occurring hind-leg paralytic disease and/or lymphoma. Both conditions are caused by an indigenous ecotropic murine leukemia virus (MuLV). These mice have a lifelong persistent viremia with total immunologic tolerance to the virus. The characteristic pathologic features are centered on the anterior-lateral horns of the lumbosacral spinal cord and consist primarily of a noninflammatory spongiform change, with reactive gliosis and neuronal dropout. The main cause of neuronal death apparently is abortive intracytoplasmic replication of virus particles. Genetic control of the naturally occurring disease in wild mice is achieved by segregation of a dominant ecotropic virus restriction gene, Akvr-1R/Fv-4R. The neurologic and/or neoplastic diseases are readily reproduced by experimental inoculation of newborn susceptible laboratory mice with purified, cloned ecotropic virus derived from the affected wild mice. The biologic and pathologic features of the experimental paralysis closely resemble those of the natural disease. This nononcogenic retroviral disease is useful in understanding the molecular basis of direct, virus-induced, neuronal and glial cell degeneration and their sequelae.