Physiological studies have demonstrated interactions of body temperature and extracellular fluid (ECF) homeostasis. As revealed by stereotaxic ablation, microtranssection or electrophysiological approaches, spino-medullary pathways and intrinsic thermosensitivity of hypothalamic neurons serve as thermal inputs, whereas activated hepato-vagal nerve fibers and hypothalamic osmosensory neurons are responsible for osmotic inputs. In rodents and ruminants, the median preoptic nucleus (MnPO) of the anterior hypothalamus represent a major site of integration for afferent signals reflecting alterations in the homeostatic systems maintaining core temperature and ECF tonicity/volume. Thus, electrophysiological studies proved osmo- and volume sensitivity of thermosensitive hypothalamic neurons. Differential activation patterns of neurons within hypothalamic nuclei under conditions of external heat or cold as well as ECF hypertonicity or hypovolemia could be demonstrated by Fos translocation analysis for the rat and sheep, with the MnPO responding to both sets of stimuli. Angiotensin II (AngII) represents an intrahypothalamic neuromodulator to enhance drinking and vasopressin release under conditions of ECF hypovolemia or hypernatremia in sheep and rats. In addition, expression of angiotensinogen within the anterior hypothalamus is up-regulated under conditions of heat exposure and AngII is partially responsible for the induction of heat loss mechanisms, possibly due to enhancement of neuronal thermosensitivity. MnPO-intrinsic neurons stimulated with AngII show enhanced firing rate, Fos nuclear translocation and intracellular calcium signaling, thus making the MnPO the prime candidate for hypothalamic thermo-osmo interaction and AngII one of the neurmodulators involved.