To investigate central neural pathways involved in release of vasopressin and in fluid electrolyte regulation, a retractable wire knife was used to make coronal knife cuts posterior to the organum vasculosum lamina terminalis (OVLT). 4 days following cuts or control surgery, animals were housed in metabolism cages and: (1) deprived of food and water for 48 h; (2) deprived of water only for 48 h; or (3) allowed continuous access to food and water. Water ingestion, food ingestion, urine volume, sodium excretion and urine osmolality were recorded daily. Trunk blood was then collected following decapitation for determination of plasma vasopressin, sodium, and protein concentrations, and osmolality. Animals with knife cuts and ad libitum access to food and water had significantly higher plasma osmolality (310 +/- 2 mosm/kg), and plasma vasopressin concentration (2.02 +/- 0.5 microunits/ml) than controls (306 +/- 1 mosm/kg and 0.60 +/- 0.04 microunits/ml, respectively). When rats were deprived of both food and water, there were no significant differences between the two groups in plasma vasopressin concentration, although plasma osmolality wa higher in animals with cuts. However, rats with knife cuts deprived of water only had significantly higher plasma osmolality (358 +/- 8 mosm/kg), sodium (164 +/- 19 mEq/l) and vasopressin (17.7 +/- 4 microunits/ml), than similarly treated control animals (317 +/- 1 mosm/kg, 145.5 +/- 1.0 mEq/1, 5.5 +/- 3 microunits/ml, respectively). These data indicate that a neural pathway in this brain region is critical for normal fluid and electrolyte balance during ad libitum access to food and water, and during water deprivation.