I. Introduction THE MECHANISMS involved in cellular response to a particular hormone-receptor interaction are complex. The intricacy of these biological systems stems from the fact that cells are multicomponent. The classical biochemical approach of isolation and characterization of proteins does not always reveal the transient interactions that occur in the natural environment of the cells. Photoaffinity labeling provides an important experimental tool for the detection and isolation of membrane components (e.g., binding sites for hormones) and for the elucidation of interactions involved in biological processes at the molecular level (1–9). This review describes some properties of photoreactive cross-linking reagents and the applications of photoaffinity derivatized hormones to highlight the potential uses of this technique for studying complex biological systems. These include: identification of receptor macromolecules; photoaffinity inactivation of receptors; persistent activation of biological functions; and localization and cellular processing of receptors. II. Photoreactive cross-linking reagents The most useful and widely used cross-linking reagents are the photoactive aryl azides which have the convenient property of becoming reactive only after photolysis.