Interaction of 148 sera from HIV-1-infected Russian patients with three synthetic peptides that mimic various V3 loop sequences of the South Russia subtype G and eight peptides with point substitutions was studied by ELISA. A sizable portion of the sera, especially those of subtype C, interacted with the peptides. The central tetrapeptide GPGQ was found to be crucial for binding to the subtype C sera. The V3 epitope antigenicity of most subtype B variants was largely determined by glycine in the first position of the central motif and the flanking residues.