In the 1950s and 1960s, several inherited disorders of fluid and electrolyte metabolism were described in which the principal disturbance appeared to be a specific functional defect in the renal tubule. For most of these diseases, plausible physiologic explanations were presented, some more convincing than others. In the past five years, genetic and molecular approaches have elucidated the underlying molecular defects in several of these disorders. In some instances, predictions based on the initial physiologic studies have been confirmed; in others, the molecular answer has come as a surprise, raising further questions about the physiology of epithelial function. In several . . .