A growing body of evidence indicates that in some cases, peptide hormones can function in the intracellular space. These findings are reviewed. In addition, this laboratory has made proposals regarding the origin, nature and function of intracrines--that is, intracellularly acting peptide hormones that also function in an autocrine, paracrine or endocrine manner. Here, these hypotheses are developed, and potential implications/applications of this point of view are discussed. Possible implications for cellular differentiation, cellular memory and hormonal responsiveness, as well as for the assumption of novel functions by intracellular regulatory proteins are discussed.