The pathogenesis of HIV-1 and HIV-2 vary to a fair degree although the 2 viruses share some homology (40%) at the nucleic acid level. Specific viral determinants may govern the different pathogenecities of these viruses in their host cells. We have initiated studies involving the construction of recombinant viruses that have a single gene replacement of a given virus type. Target sequences that are currently being investigated are the LTR, tat, rev, env, gag and pol genes. These recombinants will be transfected into the host cell and the effects of these substitutions on viral replication will be studied.