This review describes the pathogenesis of a slowly progressive disease complex caused by naturally occurring nononcogenic retroviruses in sheep and goats. In nature, infections are usually clinically silent, but disease may manifest itself after prolonged incubation periods. Clinically, this is seen as dyspnea, progressive paralysis, and/or progressive arthritis. In all organs the basic lesion is inflammatory with infiltration and proliferation of lymphocytes, plasma cells, and macrophages. Other organ-specific pathologic changes such as primary demyelination in the central nervous system and degeneration of cartilaginous structures in joints accompany inflammation. The viruses infect tissue-specific macrophage populations in vivo. Viral replication in these cells is restricted to minimal levels but continues indefinitely in the animal as a result of either failure to induce specific neutralizing antibodies or antigenic drift when neutralizing antibodies develop. Consistent low-grade viral replication sets the pace for disease by providing continuous antigenic stimulation for the inflammatory cellular immune response or antibodies that localize in the target tissues. These cells and immune complexes may have adverse effects on indigenous cell populations.