The present investigation is concerned with determining the role of calcium, phospholipids, and phospholipid metabolites on transepithelial sodium and water transport in response to antidiuretic hormone (ADH). These studies utilize the frog skin for determining sodium transport and amphibian urinary bladder for water flow measurements and scanning electron microscopy of cell surface morphology. The results demonstrate that phospholipids and phospholipid metabolites containing arachidonic acid stimulate transepithelial sodium transport through amiloride sensitive channels and the action of these lipids involves the synthesis of prostaglandins. These lipids also inhibited the increase in water flow induced by ADH, and this effect was prevented with prostaglandin synthesis inhibitors. Prostaglandins alter intracellular calcium concentrations and agents effecting calcium metabolism alter cell surface morphology and the changes in surface substructure induced by ADH. These observations support the hypothesis that alterations in membrane permeability to water and ions may involve metabolism of membrane phospholipids and prostaglandin biosynthesis.