AbstractThe molecular heterogeneity of gastrointestinal hormones is reviewed. The phenomenon of heterogeneity is characteristic of all secreted proteins, including macromolecules like albumin and immunoglobulins, as well as protein and polypeptide hormones. Heterogeneity reflects basal mechanisms involved in ribosomal biosynthesis, posttranslational cleavage and modification, as well as degradation in peripheral tissue of biologically important substances. Thus far, all gastrointestinal hormones have displayed heterogeneity. The degree of heterogeneity reported has varied for the individual gut hormones. The most extensively studied hormones, such as gastrin and insulin, have displayed a high degree of heterogeneity, and similar heterogeneity will probably emerge for the remaining hormones when they have been studied in greater detail. Based on the extent of molecular difference, a distinction between macro‐ and microheterogeneity is proposed. Macroheterogeneity indicates a difference in molecular size of several (two or more) amino acids, while microheterogeneity indicates modifications of single amino acid residues. Molecular heterogeneity has implications regarding extraction, measurement, and evaluation of the action of the individual gut hormones. Thus, extraction may require several different procedures in order to identify all the molecular forms of a hormone. Measurement in blood and other biological fluids requires careful evaluation of the specificity of the assays towards the different molecular forms of a hormone in order to evaluate its physiological role. Consequently, understanding of the significance of gut hormones in gastrointestinal disease requires further clarification of their heterogeneous nature.