We investigated the effects of three doses of diethylenetriamine (DET; 0.1-1-10 nmol/rat), putative ligand at the polyamine site on NMDA receptors, on blood pressure increase induced by N-methyl-D-aspartate (NMDA, 2 nmol/rat) microinjected at the periaqueductal gray (PAG) matter. Said doses of DET did not modify basal arterial blood pressure. Pretreatment with DET, depending on the dose used, either potentiated (DET, 0.1 nmol/rat), reduced (DET, 1 nmol/rat) the NMDA effects or left them unchanged (DET, 10 nmol/rat). DET 10 nmol/rat, microinjected 5 min before spermidine (SPD, 0.02-2 nmol/rat), significantly antagonized SPD modulation on the NMDA-induced pressor changes. These data, in agreement with the functional findings in vitro, suggest that also in vivo DET has pharmacological activities quite different from a pure antagonist but shows multiple actions on the NMDA receptors.