Abstract: Compositions comprising peptide analogues of a CD4 epitope capable of interacting with a monoclonal antibody designated Leu3a or with the envelope glycoprotein (gp120) of the human immunodeficiency virus (HIV) are provided. In a preferred embodiment, the peptide will consist of the amino acid sequence: ser-lys-leu-asn-asp-arg-ala-asp-ser-arg-arg-ser-leu-trp-asp. The invention also includes a series of peptides having one or more D-amino acid substitution that confer enhanced resistance to degradation in serum. Pharmaceutical compositions and methods for using the peptides in therapeutic applications are also provided.