Systematic analysis of structure and biological activity of peptide components of tissue extracts and biological fluids allows us to formulate a novel concept of a peptidergic regulatory system, complementary to the conventional regulatory systems (i.e. nervous, endocrine and paracrine systems). According to that concept, the proteolytic degradation of tissue proteins carried out by a specific and regulated system of tissue-specific enzymes and protein substrates gives rise to a large group of peptides, which we define as tissue-specific peptide pool. As a result, functional proteins provide their proteolytically derived fragments for maintaining tissue homeostasis.z 1998 Federation of European Biochemical Societies.