There is evidence that many peptide growth factors and hormones act in the intracellular space after either internalization or retention in their cells of synthesis. These factors, commonly called intracrines, are structurally diverse while sharing some common functional features. Reports of intracellular peptide hormone binding and action are reviewed here. Also, this laboratory has made proposals regarding the origin and actions of intracrines and these areas are further explored. Intracrine interactions and the relationship of intracrines to transcription factors are discussed. The intracellular/intracrine renin-angiotensin system (iRAS) is reviewed to illustrate the intracrine analogue of a well-established physiological system. The role of intracrine action in metazoan development is also considered. Copyright 2003 Wiley Periodicals, Inc.