We have studied the development of the antibody response to the surface glycoprotein gpl20 of human immunodeficiency nbsp; p24 antigen and infectious-virus titers in the peripheral blood had declined Whether anti-gpl20 antibodies present at undetectable levels are involved in clearance unresolved. Among the earliest detectable virus type 1 in three individuals who presented with primary human immunodeficiency virustype 1 infection syndrome. Serum anti-gpl20 antibodies were first detected 4 to 23 days after presentation, aftermanyfold from their highest values.of viremia remainsanti-gpl20 antibodies were those to conformationally sensitive epitopes; monoclonal antibody to a discontinuous epitope these antibodies were able to block the binding of gpl20 monomers to soluble CD4 or to a humanoverlapping the CD4-binding site. Some of these antibodies were type specific to a degree, in that they were more effective at blocking ligand binding to autologous gpl20 than to heterologous antibodies able gpl20. However, the appearance of these antibodies did not correlate with that ofto neutralize the autologous virus in vitro by a peripheral blood mononuclear cell-based assay. Antibodies to the V3 loop were detected at about the same time as, or slightly later than, those to the CD4-binding site. There was a weak correlation between the presence of antibodies to the V3 loop and autologous virus-neutralizing individual activity in two of three individuals studied. However, serum from the thirdcontained V3 antibodies but lacked the ability to neutralize the autologous virus in vitro, even immediately after seroconversion. Thus, no simple, universal correlate of autologous virus-neutralizing activity in antibody interactions a peripheral blood mononuclear cell-based assay is apparent from in vitro assays that rely on detectingwith monomeric gpl20 or fragments thereof.