Throughout the world, autosomal dominant polycystic kidney disease (ADPKD) accounts for 5 to 10% of patients who require renal replacement therapy. It therefore is a leading cause of ESRD. It is genetically heterogeneous. The two genes so far identified, PKD1 and PKD2, are thought to interact in renal cells, one major function being regulation of intracellular calcium. Grantham and colleagues (1,2) had postulated that increased cAMP concentrations result from altered intracellular calcium homeostasis and are involved in creating the proliferative and secretory phenotype characterizing cyst wall epithelial cells in contrast with the inhibitory effect of cAMP in the normal kidney cortex. Agonists that increase cellular cAMP, e.g., arginine vasopressin, prostaglandin E2, catecholamines, and cyst-activating factor, a neutral lipid isolated from cyst fluid (3), have the potential to stimulate cyst proliferation and fluid secretion into the cyst. In this context, it is of considerable interest that—in contrast to previous opinion—it is currently thought that the vast majority of the cysts stain for collecting duct markers and are derived from collecting ducts (4), the major target for arginine vasopressin in the nephron. It is also of note that a defect of urinary concentration is one of the earliest manifestations of ADPKD (5). In previous studies, inhibition of the vasopressin V2 receptor coupling with adenyl cyclase had interfered with formation and growth of cysts. This was seen in experimental models of renal cyst formation that were orthologous to human autosomal recessive PKD and nephronophthisis, respectively (6). The present study (7) carried this one step further by studying an animal model of ADPKD that is even more relevant to the most prevalent form of PKD in humans. The authors investigated Pkd−/tm1Som mice, which are orthologous to PKD2 in humans. In these animals, the molecular machinery of renal cAMP, aquaporin-2, and V2 receptor was upregulated. The V2 receptor antagonist OPC31260 was administered in the diet between 3 and 16 wk of age. This agent reduced renal cAMP, aquaporin-2, and the V2 receptors. Of note, however, treated animals also had lower kidney weight, blood urea nitrogen, cyst number, and markers of mitosis and apoptosis. Within the sensitivity of this animal model, no major side effects were noted. Obviously, at least in this animal model, the vasopressin V2 antagonist interfered with development and progression of ADPKD. V2 antagonists are studied extensively in hyponatremic states (heart failure, liver cirrhosis) and have a relatively good safety profile, presumably because of their high renoselectivity (8). The above experimental findings also make them hot candidates for controlled studies to interfere with the progression of ADPKD in humans.