Antidiuretic hormone (ADH) increases the permeability of the distal nephron to water. Water reabsorption in this part of the kidney occurs in response to ADH provided an osmotic gradient from tubule lumen to blood is present. The toad urinary bladder has been used extensively as a structural and functional analogue of the distal nephron for assessing the mechanism of action through which the hydrosmotic response to ADH is achieved. This tissue was used in the.present study to evaluate the possibility that ADH action involves regulation of water permeability not only by altering the luminal plasma membrane barrier of cells forming the mucosal surface of this tissue, but also regulation of one or more resistances beyond or """"""""distal"""""""" to this site. Previous freeze fracture studies which have defined luminal membrane water permeability in morphologic terms, suggest that this may be a valid hypothesis. The current experiments demonstrate directly the validity of this hypothesis and provide insight about the functional nature of the intramembrane structural entities that gain appearance in the luminal membrane in response to ADH and are considered as sites for transluminal membrane water movement.