N-Methyl-D-aspartate (NMDA) receptors were expressed in Xenopus oocytes by injecting rat brain mRNA. NMDA-elicited responses in the oocytes were measured by the voltage-clamping method. The following measurements were made in the presence of 50 microM glycine (Gly) to establish the relationship between the NMDA concentration and the current: (1) the NMDA-induced membrane current before desensitization; (2) the NMDA-induced membrane current after desensitization equilibrium; (3) the fraction of the active form of the receptor after desensitization equilibrium in the presence and absence of 50 microM Gly; (4) the rate of the recovery of desensitized receptors upon removal of NMDA. Gly was essential for not only the activation of NMDA receptors but also their desensitization. These results were analyzed on the basis of a minimal model where one agonist and one Gly binding site were assumed. The equilibrium and rate constants of the model were evaluated for NMDA in the presence of saturating amounts of Gly. This model will be useful for systematically explaining the complicated responses of NMDA receptors.