A number of studies have been initiated to study the role of the variable region 3 epitope (V3) of the HIV-1 envelope in eliciting neutralizing antibodies. A series of ELISA assays have been developed to measure binding antibodies to synthetic peptide analogs representing the 3 neutralization epitope of the HIV-1 envelope glycoprotein. The peptides correspond to the specific amino acid sequences that have been determined for 4 strains of HIV-1 (IIIB, MN, RF, Z3). These assays have been used to study the relationship of these specific antibodies to in vitro neutralization of virus. In a study of the geographic diversity of antibody responses, binding antibody titers and neutralizing antibody titers were compared in sera from the U.S., Brazil, Haiti, and Zaire. In another study to determine whether variation in neutralization epitopes in chronic infection are associated with changes in the V3 region, sequential serum samples from five infected individuals were titered for neutralizing and binding antibodies. The peptides have also been tested for their ability to block neutralization of homologous and heterologous virus strains. These studies indicate that the V3 domain is an important neutralization epitope, but that a cross-reactive epitope outside this region may also exist.