Integrins are the major class of receptors by which cells interact with the extracellular matrix, promoting cell adhesion and cell migration. Signaling from extracellular matrix molecules to the interior of cells can occur via integrin receptors. These signaling events are thought to play roles in processes important for embryonic development such as tissue organization, cell migration, and protease secretion. Integrins generally contain two relatively short cytoplasmic domains. The roles of these domains in controlling the location of receptors, signaling, and regulating cell behavior is being explored using molecular biology and biochemical methods. Functions of isolated domains are being tested using chimeric receptors containing a reporter domain consisting of a subunit of the interleukin-2 receptor and various integrin cytoplasmic tails. The beta1, beta3, and to some extent beta5 integrin cytoplasmic domains were found to contain sufficient information for the targeting of receptors to adhesion sites of cells, whereas the alpha5 and alternatively spliced version of the beta3 integrin do not. Further studies are characterizing the roles of integrin cytoplasmic domains in regulating messenger systems involving tyrosine phosphorylation, calcium concentration, and pH. Overexpression of certain cytoplasmic domain chimeras was able to produce a dominant negative phenotype. The beta1 and beta3 cytoplasmic domains can inhibit cell spreading and localization of endogenous fibronectin receptors to extracellular matrix contacts with fibronectin fibrils; the alternatively spliced beta3 and beta5 cytoplasmic domain chimeras could not. These studies demonstrate the central role of certain specific integrin cytoplasmic domains in cellular functions. They should help provide an in-depth understanding of how cells communicate with their extracellular environment in normal and abnormal embryonic development, where such signaling is essential for coordinating the complex rearrangements and final organization of oral, facial, and other developing tissues. These interactions are also likely to be important for adult tissue repair.