N-methyl-D-aspartate receptors (NMDAR) are part of the ionotropic glutamate receptor family and are important in several physiological and pathophysiological processes in the mammalian central nervous system. The binding of both glutamate and the co-agonist glycine in order to activate NMDAR opening is a unique property of this receptor type. Consequently, various endogenous ligands at the NMDAR glycine-binding site such as D-serine have been studied extensively and are thought play important roles in synaptic function (Paoletti & Neyton, 2007). Moreover, the clinical use of NMDAR-glycine site agonists or glycine uptake transporter antagonists has been explored as these actions may be expected to enhance excitatory neurotransmission mediated by NMDARs in the central nervous system and could alleviate the hypofunction of NMDARs implicated in schizophrenia (Lane et al. 2005). One such agonist that is undergoing clinical trials is sarcosine (N-methylglycine) an endogenous amino acid in the brain that takes part in the metabolic pathways of glycine biosynthesis and metabolism. Sarcosine is a substrate inhibitor of the Type I glycine transporter (GlyT1) but also acts as an NMDAR co-agonist (Zhang et al. 2009). The mechanism of NMDAR activation by sarcosine remains to be elucidated and the purpose of this study was to improve our understanding of NMDAR activation by sarcosine. Macroscopic and single channel NMDAR currents were recorded from Xenopus laevis oocytes expressing recombinant GluN1 and GluN2B subunits. Dose-response curves from oocytes injected with recombinant NMDARs in the presence of saturating concentrations of glutamate demonstrated that sarcosine (sarcosine EC50=28.1 ± 2 µM, n=8) was approximately 100-fold less potent than glycine (glycine EC50=0.2 ± 0.01 µM, n=5). Furthermore, the maximal response exhibited by sarcosine at 300 µM was approximately 20 % lower than the maximal response evoked by saturating (50 µM) concentrations of glycine. These data confirm that sarcosine is acting as a partial agonist (relative to glycine) at GluN1/GluN2B NMDARs. Single channel recordings show that sarcosine did not significantly change the amplitude or duration of individual channel openings relative to glycine and that the partial agonism exhibited by sarcosine results from a combination of reduced channel open probability during the receptor activation and shortened duration of receptor activation.