Neurons of the organum vasculosum of the lamina terminalis (OVLT) are necessary for thirst and vasopression secretion during hypersmolality in rodents. Recent evidence suggests the osmosensitivity of these neurons is mediated by a gene product encoding the transient receptor potential vanilloid-1 (TRPV1) channel. The purpose of the present study was to determine whether mice lacking the TRPV1 channel had blunted thirst responses and central Fos activation to acute and chronic hyperosmotic stimuli. Surprisingly, TRPV1-/- versus wild-type mice ingested similar amounts of water after injection (0.5 mL, sc) of 0.5 M NaCl and 1.0 M NaCl. Chronic increases in plasma osmolality produced by overnight water deprivation or sole access to a 2% NaCl solution for 48 hrs produced similar increases in water intake between wild-type and TRPV1-/- mice. There were no differences in cumulative water intakes in response to hypovolemia or isoproterenol. In addition, the number of Fos-positive cells along the lamina terminalis including the OVLT as well as the supraoptic nucleus and hypothalamic paraventricular nucleus was similar between wild-type and TRPV1-/- mice after both acute and chronic osmotic stimulation. These findings indicate that TRPV1 channels are not necessary for osmotically-driven thirst or central Fos activation, and thereby suggest that TRPV1 is not the primary ion channels that permits the brain to detect changes in plasma sodium concentration or osmolality.