Studies were carried out in the rat to investigate whether glutamic acid is involved in the regulation of vasopressin (VP) release. For this purpose plasma VP levels were measured in rats treated with the glutamate agonist N-methyl-D-aspartate (NMDA). In our experimental conditions NMDA induced dose-related increases in plasma VP levels in normohydrated rats. The effect of NMDA were prevented by 3[(+)-2 carboxy-piperazine-4-yl]propyl-1-phosphonic acid (CPP), a selective and competitive antagonist of NMDA receptors. These data show that glutamate may contribute to the physiological release of VP from the neurohypophysis.