We sought to determine whether conjugation methods could improve the immunogenicity of human immunodeficiency virus (HIV)-1 gp120 and env2-3, a nonglycosylated form of gp120. Conjugate vaccines were created by coupling tetanus toxoid (TT), gp120, and/or env2-3 with group B streptococcal type III polysaccharide (III) by reductive amination. Size-exclusion chromatography revealed polymers larger than those of the uncoupled proteins after conjugation. Geometric mean titers of gp120-specific immunoglobulin G (IgG) in serum from mice given env2-3-TT-III or env2-3-gp120-TT-III conjugates increased from <50 before to 3031 and 4756, respectively, after vaccination, whereas an uncoupled mixture of gp120, TT, and III, and III-TT not coupled with gp120 or env2-3 were poorly immunogenic. Pooled serum diluted 1rcolon;20 from mice given env2-3-gp120-TT-III inhibited infection of HIV-1(MN) of Sup-T1 cells and demonstrated neutralizing activity against infection with primary isolate HIV-1(BR014). HIV-1 gp120-specific IgG with neutralizing activity against HIV-1 can be induced with conjugates containing gp120, env2-3, III, and TT.