We have continued studies on the interaction of CD4 and gpl2O molecules and heir role in HIV infection and immunopathology. Ongoing studies include the anal is of autoantibodies to CD4 in HIV positive sera, the role of antibodies to HI in blocking soluble CD4 binding to gpl2O, and the mechanism of action of the antiviral compound dextran sulfate. Autoantibodies to CD4 from HIV positive serum have been analyzed for epitop specificity and cross reactivity. Affinity purified antibodies recognize th fourth extracellular domain on CD4 at sites which are not exposed on cell s face CD4. Antibodies from several individuals bind to at least two common epitop as demonstrated by antibody competition data. These antibodies appear to devel as a consequence of aberrant CD4 processing secondary to HIV replication. Antibodies to gpl2O which block the binding of CD4 have been further charac rized using a number of in vitro assays. These antibodies are cross reactive with variety of HIV strains and correlate with the neutralization titer. The epi pes- seen on gpl2O are conformationally dependent and may represent broadly cons ved potential neutralizing sites. Finally, we have defined the molecular mechanism for polyanionic polysaccha de antiviral activity. These compounds do not block the Interaction of CD4 and pl2O in a number of binding assays, but instead interfere with the immunodominan V3 neutralizing loop as demonstrated by the potent inhibition of monoclonal antibodies binding to this gpl2O site. This mechanism suggests that compoun with this mode of action but with better oral absorption properties will be usef anti-HIV agents.