An hypothesis has been developed to rationalize the evolution of regulatory peptides. In order to account for critical relationships involving peptide regulators, their receptors, and peptide processing enzymes, the following generalizations will be supported: (1) peptides arose from protein precursors as proteolytic digestion by-products and acquired hormonal status during the course of natural selection; (2) initially, peptides served primarily nutritional roles, thereby permitting increased growth rates and reproductive advantages for recipient cells; (3) specific peptide sequences were conserved during evolution and were associated with biological activities which were essential for survival of species as divergent as unicellular organisms, amphibians, and mammals; and (4) regulatory peptides probably arose simultaneously with their membrane-oriented, macromolecular receptor sites. In support of the conservation of sequence information or function, or both, during evolutionary development, evidence has been obtained to indicate that peptide sequences which occur in two classes of amphibian peptides appear to be extensively conserved in mammals. Studies with an antiserum directed against the N-terminal sequence of amphibian physalaemin have permitted the recognition of a mammalian octapeptide which exhibits 80% homology with residues 1-5 in that region. Another study with an antiserum directed against the midregion (sequence 5-8) of amphibian bombesin has indicated the existence of milk peptides which mimic bombesin in several pharmacological bioassays. These studies indicate that radioimmunoassays can be powerful tools in facilitating recognition of peptide sequences conserved throughout evolution.