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A 37-year old man had suffered palmar hyperhidrosis since he was fifteen years old. In the last year, he has been treated with tolvaptan for autosomic polycystic kidney disease (ADPKD). The start of tolvaptan therapy was associated with a complete resolution of palmar hyperhidrosis and a sensation of relaxation. During the year on which the patient took tolvaptan, he had to suspend the drug twice. The suspension of tolvaptan was associated with the reappearance of palmar hyperhidrosis followed by sudden remission after the drug reintroduction. Palmar sweating also known as ‘emotional sweating’ is not related to thermoregulation but allows an adequate adjustment of the frictional force to perform fine hand movements. Palmar hyperhidrosis is a chronic neurologic disorder characterized by excessive sweating of eccrine glands due to overactivity of the sympathetic nervous system. Palmar sweating and emotional processing are controlled by the limbic system. In this case report reduction of palmar sweating was associated with a sense of well-being. Corticotropin releasing factor (CRF) and adrenocorticotropic hormone (ACTH) are the two main hypothalamic hormones that interact with both the limbic system and the peripheral sympathetic nervous system. Tolvaptan is an arginine vasopressin (AVP) antagonist. AVP has effects on the sympathetic nervous system through both central and peripheral actions. Centrally AVP is a well-known ACTH secretagogue. Remission of palmar hyperhidrosis is probably mediated by tolvaptan acting on central ACTH secretion.