The immunological cross‐reactivity of several peptides with specific pattern‐property characteristics related to the epitopes of human immunodeficiency virus type 1 (HIV‐1) gp160/ 120 envelope proteins has been investigated. Proteins with similar primary structures can be expected to show functional or topographic similarities, such as specific epitopes which may cross‐react with antibodies derived from the immunisation of animals with other members of the same protein family. These structure‐function characteristics may be revealed as periodicities derived from presentations based on the discrete Fourier transformation of the distributions of various physico‐chemical amino acid descriptors, constituting the polypeptide backbone and amino acid side‐chains of the protein molecule. Such approaches, for example, have permitted prediction of periodicities corresponding to secondary structural motifs, including amphipathic α‐helices and β‐sheets, within protein sequences, and have helped to clarify potential binding sites for ligands, substrates or cofactors with interacting macromolecules. Based on this approach, characteristic periodicities have been identified which represent common Fourier transform spectral properties of the envelope (ENV) gpl60/120 glycoproteins from a range of HIV‐1 isolates. In addition, similar periodicities have been detected as components of the discrete Fourier transform representation of the corresponding amino acid descriptors of the CD4 binding domain of gpl20. Accordingly, we have synthesised several peptides having periodic characteristics in their discrete Fourier transform representations similar to these HIV‐1 proteins. These nonhomologous synthetic peptides induced cross‐reactive antibodies in New Zealand White rabbits. Polyclonal antibodies raised to one of these peptides reacted with HIV‐1 ENV gpl20‐related proteins, as determined by enzyme‐linked immunosorbent assay and Western blotting techniques. These findings provide further evidence for a role of immunological cross‐reactivity and molecular biomimicry in the development of peptide‐based vaccines directed against viral or bacterial pathogens.