It has been found that cells in the region of the supraoptic nucleus (SON) of the hypothalamus are sensitive to osmotic stimuli in a physiological range, and have studied the mechanism by which the osmotic sensitivity arises. An in vitro hypothalamic brain slice preparation has been used to make intracellular recordings from the SON. Cells lying in the SON respond to small increases (9--40 mosmol l-1) in the osmolarity of their external environment with a marked increase in firing rate. They respond to NaCl and mannitol although not to glucose. The osmotic sensitivity of SON neurones has a complex origin at both a pre- and a postsynaptic level, being composed first of depolarization of the primary SON neurone by an increase of extracellular osmolarity and second by an increased rate of occurrence of excitatory synaptic events which markedly augment firing rate. These results are consistent with Jewell and Verney's suggestion that osmoreception in the mammalian brain occurs in the region of the anterior hypothalamus, and extends this localization by indicating that the SON neurones are themselves both directly osmosensitive and part of an osmoreceptive complex.