Abstract Electrolytic ablation of the periventricular tissue surrounding the anteroventral third ventricle (AV3V) alters fluid and electrolyte regulation. In addition, these lesions produce neural degeneration in the supraoptic nucleus (SON) and neural lobe, which suggests a neural pathway from the AV3V region to the SON. To determine if pathways in this brain area may mediate some of the effects which follow AV3V periventricular ablation, food and water ingestion, urine volume, and body weight, as well as drinking responses to a number of dipsogenic challenges were determined following placement of small knife cuts between the level of the organum vasculosum lamina terminalis (OVLT) and the SON. Metabolism measurements were taken daily for 7 days following either knife cuts or control operations, and again 4 weeks after surgery. Drinking responses following subcutaneous injections of angiotensin II, water deprivation, and cellular dehydration were determined at least 2 weeks after surgery. Rats with knife cuts exhibited an increase in water ingestion and urine volume, an enhanced water consumption following water deprivation and acute cellular dehydration, and did not gain weight at the same rate as control operated rats. The hyperdipsia following cellular dehydration was abolished by bilateral nephrectomy. These data indicate that a neural pathway coursing through this brain region is critical for fluid regulation and maintenance of body weight.