The neural and endocrine bases of the generation of thirst are reviewed. Based on this review, a hierarchical system of neural structures that regulate water conservation and acquisition is proposed. The system includes primary sensory-receptive areas; secondary sensory structures (circumventricular organs), which detect levels of hormones, including angiotensin II and vasopressin, which are involved in generating thirst; preoptic and hypothalamic structures; and an area within the ventrolateral quadrant of the periaqueductal gray matter. Hodological and other data are used to determine (...) the hierarchical organization of the system. Based on studies of the effects of lesions to various structures within the hierarchy of the system, it is proposed that the awareness of thirst in rodents is either entirely or predominantly due to neuronal activities in a subsection of the ventrolateral periaqueductal gray matter. It is also hypothesized that the awareness of thirst in primates is due to neuronal activities in both the ventrolateral periaqueductal gray and in a region within the medial prefrontal and anterior cingulate cortex. (shrink)