The tight junction, or zonula occludens (ZO), forms a semi-permeable barrier in the paracellular pathway in most vertebrate epithelia. The ZO is the apical-most member of a series of intercellular junctions, collectively known as the junctional complex, found at the interface of the apical and lateral cell surface. This structure not only restricts movement of substances around the cells, but may also serve as a 'fence' acting to maintain the cell surface compositional polarity characteristic of epithelial cells. The morphology and physiology of the ZO have been well documented and are briefly reviewed here. The biochemistry of this important intercellular junction remains largely unknown, although a tight junction-specific polypeptide called 'ZO-1' has recently been identified. Preliminary observations regarding the role of this peripheral phosphoprotein in the biology of the ZO are presented.