In this study 96 15-mer peptides encompassing the entire sequence of HIV-1 gp120 were synthesized and used to immunize BALB/c mice (i) alone or (ii) in conjunction with the T helper cell determinant FISEAIIHVLHSR (FIS) from sperm whale myoglobin, which is well recognized by major histocompatibility complex (MHC) class II molecules of BALB/c. Of these peptides 39 were immunogenic per se and 57 were not. Out of the 57 non-immunogenic peptides 53 could be rendered immunogenic with the second immunization protocol. With the exception of 4 cases, the anti-peptide antibody titers induced in (ii) were equal (14 cases) or higher (78 cases) than those induced in (i). From the 96 anti-peptide antibodies tested, 12 were able to recognize recombinant gp120 with good antibody titers, a result in agreement with previously identified B cell epitopes from gp120 by anti-peptide antibodies induced with longer peptides conjugated to a carrier protein. Moreover, 4 of the 12 anti-peptide antisera that recognized gp120 were able to neutralize HIV-1 infectivity in vitro, showing that the strategy of co-immunization with FIS may afford functional antibodies.