African monkeys naturally harbor simian immunodeficiency viruses (SIVs), the potential progenitors of human immunodeficiency virus-2 (HIV-2). Asian monkeys can acquire SIV from African monkeys through close contact while in captivity. In addition, an SIV isolated from a chimpanzee has been shown to be closely related to HIV-1, the causative agent of human AIDS. Due to this evolutionary relationship between SIVs and HIVs, there is great concern regarding transmission of the virus from monkey to man via biological products (such as some vaccines) grown in monkey- derived cells. We thus undertook to analyze a variety of monkey DNAs for endogenous SIV/HIV-related sequences which might potentially generate an infectious virus. Nested PCR analysis were carried out on high-molecular-weight DNAs isolated from a Carribbean African green monkey, from Asian monkeys including cynomolgous, pig-tailed, and rhesus and from man. PCR primers were based upon highly conserved sequences in the pol regions of known SIVs and HIVs. Agarose gel analysis of the PCR products indicated amplified fragments from all species. We are currently molecularly cloning these fragments and will obtain their nucleotide sequences to determine the evolutionary relatedness of these amplified endogenous sequences to known infectious SIVs and HIVs.