Cystic maldevelopment of the kidney can occur when the normal processes of nephrogenesis are disrupted. The result is formation and enlargement of fluid-filled cysts instead of normal renal tubules. Several human disease states are associated with the development of renal cysts. Events triggered by genetic mutation or environmental insult probably lead to the combination of factors believed to stimulate cyst formation and enlargement, including epithelial hyperplasia, abnormal protein sorting, altered fluid transport, and abnormal extracellular matrix:cell interactions. A precise delineation of the cellular pathophysiology of renal cystic maldevelopment has the potential to do the following: (1) focus genetic investigation on specific "cystic" candidate genes; (2) provide models for the definitive identification of such candidate genes; and (3) provide key targets for immunotherapy or pharmacotherapy designed to prevent renal cyst formation and progressive enlargement.