A neurotropic retrovirus causes a naturally occurring lower-limb paralysis in wild mice, characterized by a noninflammatory spongiform change located primarily in the lower spinal cord. The causative agent is an ecotropic murine leukemia virus, unique to certain wild mice in southern California. The disease is readily transmitted to newborn susceptible laboratory mice. The paralytogenic property is attributed to direct viral injury to motor neurons and glial cells and is associated with unique amino acids in the murine leukemia virus envelope gp70. This murine model may have relevance to both human T-lymphotropic virus type I, and human immunodeficiency virus infection of human brain. It presents a practical model for testing antiviral agents aimed at retrovirus infection of the mammalian central nervous system. Simian acquired immunodeficiency syndrome type D retrovirus causes a silent infection of the brain in infected macaques. Viral nucleic acids are detected in the brain parenchyma in the absence of viral antigen, neurological symptoms, and neuropathology. Infected choroid plexus epithelial cells are the source of cell-free virus in the cerebrospinal fluid of viremic monkeys. This model adds yet another example of retroviral infection of the central nervous system and points to the choroid plexus as a potential source of infectious virus.