SYNOPSIS. The temporal sequence of evolution of new peptide hormones and their receptors is examined. Analysis of the evolutionary history of the vertebrate cholecystokinin/gastrin family of peptides and their receptors is used in an attempt to differentiate among hormone/receptor coevolution, delayed receptor evolution, and receptor pre-evolution as patterns of evolution leading to the generation of regulatory diversity. The evidence that cholecystokinin is the ancestral peptide in this family is reviewed and compared to he pattern of evolution of cholecystokinin and gastrin receptors in vertebrates. Evidence for delayed receptor evolution in this system is presented along with the possibility that receptor pre-evolution may also have occurred. Conspicuously, no evidence presently exists that hormone/receptor coevolution is a feature of the cholecystokinin/gastrin family. Finally, possible molecular mechanisms of linking the evolution of new hormones with the evolution of new receptors specific for those hormones are described. It is concluded that rapid progress in this field requires study of the structural properties of peptide hormone receptors.