Patients with obsessive-compulsive disorder (OCD) hypersecrete the arousal producing neurohormone arginine vasopressin (AVP) into the cerebrospinal fluid and plasma. Because OCD responds preferentially to potent serotonin uptake inhibitors, we compared the effect of chronic fluoxetine treatment to that of other antidepressants (trazodone and desipramine) on AVP release from rat hypothalamic organ culture and showed that only fluoxetine significantly reduced in vitro AVP release.