It is well-established that N-methyl-D-aspartate receptors (NMDARs) are inhibited by ethanol. However many studies that investigate the effects of ethanol on this receptor use concentrations of ethanol that would likely prove to be lethal in many individuals (100 mM and greater). To put this in context, in the UK the legal blood alcohol limit for driving a motor vehicle is 80 mg/100 ml which is equivalent to approximately 17 mM ethanol. Since NR2B-containing NMDARs are expressed earlier in neural development than NR2A-containing NMDARs, differential sensitivity of these NMDAR subtypes to ethanol may have implications for fetal exposure to ethanol during pregnancy. In our study we have examined the effects of ethanol (10, 20, 40 and 80 mM) on NR2A- and NR2B-containing NMDARs expressed in Xenopus laevis oocytes using two-electrode voltage-clamp recording techniques. Control recordings from uninjected oocytes showed that the range of ethanol concentrations used did not affect the holding current required to voltage-clamp oocytes at −40, −60 or −80 mV in either a Ca²⁺-containing or Ba²⁺-containing external recording solution (n = 11, 13 respectively). For NR1/NR2A NMDARs ethanol (40 mM) inhibited glutamate-evoked (100 μM) currents in a voltage-independent manner (mean inhibition at −80 mV = 18.2 ± 1.1%, n = 21). Similar levels of inhibition were observed for NR1/NR2B NMDARs (mean inhibition at −80 mV = 17.7 ± 1.9%, n = 17). Concentration-response curves to determine the potency of glutamate and the co-agonist, glycine (in the presence of 40 mM ethanol) at NR1/NR2A and NR1/NR2B NMDARs demonstrated that the EC₅₀ values obtained were not different from values previously reported (Erreger et al. 2007; Chen et al. 2008) for these receptor subtypes (NR2A: glut = 2.9 ± 0.1 μM, gly = 0.84 ± 0.05 μM; NR2B: glut = 1.4 ± 0.1 μM, gly = 0.74 ± 0.07 μM; n = 9, 16, 8, 8, respectively). Neither voltage-dependent Mg²⁺ block nor memantine block of glutamate-evoked currents mediated by either receptor subtype was affected by ethanol (40 mM). Thus under our recording conditions we find no evidence for a differential effect of the inhibitory action of ethanol at these two NMDAR subtypes. Reduced ethanol inhibition of NR1/NR2A NMDAR-mediated responses was observed when the carboxy-terminus of the NR2A subunit was either deleted with the sequence ending at residue Phe822 (mean inhibition at −80 mV: 11.6 ± 0.8%, n = 8) or truncated with the sequence ending at residue Iso1098 (mean inhibition at −80 mV: 10.7 ± 1.8%, n = 8). The reduced inhibition seen with these NR2A carboxy-terminus deleted and truncated constructs suggests that this region of the NR2A subunit may contain sites of interaction with ethanol.