PURPOSE Techniques that can be used to examine the molecular mechanisms of stromal-epithelial interactions are described. MATERIALS AND METHODS A historical perspective of available techniques is provided. Recent developments and examples are used to illustrate and provide descriptive literature references for these methods. Since the possibilities for manipulating experimental systems are enormous and rapidly expanding, the reader should be aware that this review is an overview of how data have been and could be obtained rather than a comprehensive listing of what has been achieved. This review focuses on studies performed in the organs of the urogenital tract to illustrate techniques that are available.RESULTS Recent technological innovations have impacted our ability to manipulate specific components and pathways of stromal-epithelial interactions. They include rapid developments in transgenic and gene knockout mouse technology, and the development of highly efficacious gene delivery and expression systems. CONCLUSIONS These technologies have the potential to transform our understanding of the mechanistic basis of intercellular communication and point the way toward new therapeutic approaches for benign and malignant proliferative conditions.