During extracellular dehydration, neural systems that sense deficits in body fluid homeostasis operate in tandem with those that mediate motivation and reward in order to promote ingestive behaviors that restore fluid balance. We hypothesized that hypothalamic orexin (Ox) neurons act as an interface to couple brain regions sensing and processing information about body fluid status with central nervous system motivation and reward systems. An initial set of anterograde and retrograde tracing experiments suggested that structures along the lamina terminalis (LT), a region of the forebrain that serves to monitor and integrate information reflecting body fluid balance, project to hypothalamic Ox neurons that, in turn, project to dopamine neurons in the ventral tegmental area (VTA). A second set of experiments determined whether Ox neuron activation is associated with extracellular dehydration and the seeking out and consumption of water and saline. An elevation of Fos-like immunoreactivity in Ox neurons was observed in fluid-depleted rats that were allowed to ingest water and sodium. A final experiment was conducted to determine whether Ox release in the VTA promotes thirst and salt appetite. Bilateral microinjection of the Ox Type I receptor antagonist SB-408124 into the VTA prior to acute extracellular dehydration attenuated fluid intake. Together, these studies support the hypothesis that structures along the LT modulate activity in the VTA through actions of orexinergic neurons that have cell bodies in the hypothalamus. This pathway may function to facilitate sustained consumption of fluids necessary for restoration of fluid balance.