Small ruminant lentiviruses (SRLV) and human immunodeficiency viruses (HIV) are related retroviruses that cause multisystem disease usually over a long period of time. The viruses show similarities and differences in biological and pathogenic features. The basic retroviral genomic organization is complicated by the presence of a variable number of accessory genes in both viruses, though the structure is more complex in HIV. Both are mucosal pathogens, and infect cells of the monocyte-macrophage lineage. The main difference in cell tropism is that, unlike HIV, SRLV do not infect lymphocytes. A major feature of both pathogens is restricted replication and virus latency, which are partly responsible for the establishment of chronic infection usually lasting for life. The pathologies observed are similar in the early stages of both infections, and possibly following highly active anti-retroviral therapy (HAART). While the pathogenesis of HIVinduced disease during symptomatic stages is mainly due to secondary infections and neoplastic conditions, the early and post-HAART stages are associated with chronic inflammatory changes that resemble those found in SRLV diseases which are thought to be mediated by anti-virus immune responses.