Most candidate human immunodeficiency virus (HIV)-1 vaccines induce antibodies that neutralize T cell line-adapted HIV-1 strains. Until recently, however, no neutralizing activity against primary HIV-1 isolates had been demonstrated in sera from human vaccinees. Since most candidate HIV-1 vaccines have been constructed from T cell line-adapted syncytiuminducing (SI) strains, experiments were done to test whether sera from recipients of SI-based vaccines could preferentially neutralize SI primary HIV-1 isolates. Various neutralization assays were performed with sera from volunteers receiving ALVACgp160MN and/or rgp120SF2. Neutralizing activity was detected against 4 of 8 SI primary isolates but against none of 5 non-SI primary isolates. The data suggest that, for the induction of neutralizing antibodies to a broad array of HIV-1 primary isolates, a polyvalent vaccine will be needed containing representatives of more than a single category of viruses.