Lentiviruses of sheep, goats, and primates are a genetically distinct group of retroviruses that replicate in immune cells and usually cause disease with a long latent period and slowly progressive course, often leading to death. In order to understand how these viruses interact with their hosts and cause pathological change, as well as developing improved diagnostic and therapeutic methods, a molecular analysis of several of these viruses in being carried out. Sequence analysis of molecular clones of caprine arthritis encephalitis virus (CAEV) and equine infectious anemia virus (EIAV) revealed that the complex genomic organization observed with HIV and visna is common to all lentiviruses and suggests that their extra genes, such as tat, art, and sor, must be an important part of how these viruses interact with their hosts. We have developed sensitive ELISAs, using viral protein produced in bacteria, to detect antibodies to CAEV and EIAV, which are superior to existing assays. We have also determined that the replication of lentiviruses, and other retroviruses as well, can be effectively inhibited by 2',3'-dideoxynucleosides, which act to terminate the synthesis of retroviral DNA during reverse transcription of the viral genomic RNA. Currently, additional drugs are being evaluated to determine if they are superior to the dideoxynucleosides, or can be used in combination. Animal studies, using both mice and goats, have been initiated to determine optimal ways in which such drugs can be used to control viral spread and virus-induced disease. It is hoped that such studies will represent an important model for the use of such drugs on AIDS patients.