Like other hormonally mediated mechanisms, maintenance of body fluid osmolality requires integrated responses from multiple signals at various tissue locales, a large number of which are open to modulation by circulating endocrine factors including the ovarian steroid, oestrogens (E(2)). However, the precise mechanism and the site of action of E(2) in regulating fluid osmolality are not properly understood. More importantly, the biological significance of this action is not clear and the physiological circumstances in which this modulation is engaged remain incomplete. The demonstration of oestrogen receptors (ER) in neural tissues that bear no direct relation to reproduction led us to examine and characterise the expression of ER in brain nuclei that are critical for the maintenance of fluid osmolality. In the rat, ERbeta is prominently expressed in the vasopressin magnocellular neuroendocrine cells of the hypothalamus, whereas ERalpha is localised extensively in the sensory circumventricular organ neurones in the basal forebrain. These nuclei are the primary brain sites that are engaged in defense of fluid perturbation, thus providing a neuroendocrine basis for oestrogenic influence on body fluid regulation. Plasticity in receptor expression that accompanies fluid disturbances at these central loci suggests the functional importance of the receptors and implicates E(2) as one of the fluid regulating hormones in water homeostasis.