To examine the role of receptor changes in the adaptive response to physiological stimulation, the density and distribution of excitatory amino acid receptors within the hypothalamus and other brain regions were examined in rats deprived of water for 2 days. Membrane binding assay revealed an increase in glutamate receptor density and a small shift in the affinity of glutamate for the receptor. Regional analysis of these changes by receptor autoradiography specific for NMDA, non-NMDA or metabotropic glutamate receptor binding indicated that NMDA and metabotropic receptor densities are increased in the brain. Regional increases were found principally for the NMDA receptor binding within the supraoptic nucleus, anterior hypothalamus, caudate-putamen and globus pallidus with no significant changes in 24 other brain regions. No significant changes were found in any brain regions for AMPA receptors. Metabotropic and kainate receptors tended to parallel the NMDA receptor changes, although few regions reached statistical significance. These changes indicate that brain regions associated with water balance regulation show selective adaptive increases in NMDA receptors during water deprivation which may facilitate prolonged activation of these cells.