Although previous studies have demonstrated that water immersion to the neck (NI) results in a significant diuresis, the mechanisms are incompletely delineated. Because recent studies in our laboratory have demonstrated that NI is associated with a suppression of antidiuretic hormone (ADH), it is possible that such a suppression mediates the encountered diuresis. The present study was undertaken to assess more directly the relative role of ADH suppression by determining the effects of vasopressin administration. Six hydrated normal subjects were studied on two occasions while undergoing 6 h of NI. During the second NI study, aqueous vasopressin (20 mU/h) was infused for the initial 4 h of study (NI + vasopressin). NI resulted in a significant increase in urinary flow rate beginning during hour 1 and persisting throughout NI. In contrast, during NI + vasopressin, the anticipated diuresis was abolished throughout the 4 h of vasopressin administration. Cessation of vasopressin administration during the final 2 h of NI + vasopressin resulted in a marked and prompt diuresis. The present observations are consistent with the formulation that ADH suppression participates importantly in mediating the diuresis of NI in hydrated normal subjects.