The goal of this proposal is to further define at the molecular level HIV-1 envelope structures and human cell structures mediating virus entry into the host cell. We will focus on the molecular definition of fusion/entry structures using novel fusion blocking reagents that we have developed. Recent studies have demonstrated that HIV-1 virus entry is not mediated through receptor mediated endocytosis but occurs directly through virus fusion events localized at the plasma membrane. Therefore, fusion studies are an appropriate model for HIV-1 entry into cells. This proposal utilizes both anti-viral and anti-host cell antisera to define on a molecular basis fusion peptides. The identification of structures directing cellular fusion processes of HIV-1 virus represent new avenues for vaccine development and therapeutics. Our long term goal is to determine the utility of these structures for immunological manipulations which productively alter HIV viral induced pathogenesis. It is likely that such viral and cellular structures will have implications beyond HIV-1 virus infections.