The control of suckling-induced bursting activity of oxytocin neurons and of phasic activity of vasopressin neurons by N-methyl-D-aspartate receptors was investigated in anaesthetized lactating rats. Receptor antagonist or agonist was applied in the vicinity of supraoptic neurons recorded extracellularly. The basal activity of oxytocin neurons was tonically decreased and increased by sustained application of the antagonist and agonist respectively. These effects occurred independently of the effectiveness of suckling to trigger the bursting pattern. When drugs were applied during an ongoing series of milk-ejection-related bursts, these changes were accompanied by parallel modifications in burst amplitude, but burst periodicity was unaffected. In rats failing to milk-eject, antagonist or agonist application did not facilitate the occurrence of bursts. Simultaneous recordings from oxytocin neurons in the contralateral supraoptic nucleus showed that neither their basal nor their bursting activity were affected, indicating the absence of cross-talk between nuclei during such application. The excitatory effect of N-methyl-D-aspartate differed from that induced in the same neurons by i.c.v. injection of oxytocin, which enhanced basal level of activity and burst amplitude, but also increased burst frequency. Furthermore, the distribution of interspike intervals indicated that N-methyl-D-aspartate, but not oxytocin, induced a regularization of the spike pattern. For vasopressin neurons, application of the receptor antagonist inhibited phasic activity by decreasing burst duration and increasing silences. Conversely, N-methyl-D-aspartate enhanced phasic activity, increasing both the duration of the active phases and the frequency of spikes during active phases. When applied to silent vasopressin neurons, N-methyl-D-aspartate induced a regular phasic activity. These results provide evidence that functional N-methyl-D-aspartate receptors regulate the excitability of both oxytocin and vasopressin neurons in lactating rats. These receptors play a paramount role in maintaining a certain level of basal activity which will favour appropriate discharge patterns, tonic for oxytocin neurons and phasic for vasopressin neurons. For oxytocin neurons, this sustained control by ambient glutamate influences the amplitude of bursts, but N-methyl-D-aspartate receptors are probably not involved in the generation of the bursting pattern.