We have previously demonstrated that a 23-amino acid peptide derived from the V3 loop of the surface glycoprotein of the HIV-1 strain MN is able to bind CD4 and to enhance HIV-1 infection. Further studies have suggested that the peptide/CD4 interaction induces an increase in both CD4 expression and CD4/gp120 binding affinity. This paper describes the biological and physico-chemical characterization of three analogues of reduced sequence that have been designed in order to identify the minimum active sequence of this peptide corresponding to the MN-HIV- 1 principal neutralizing domain. Biological studies indicate that the entire sequence is required for biological activity and that the sequence 1-18 presents an inhibitory activity. CD and FT-IR absorption data are discussed here in order to identify possible structure-function correlations.