1. Whole‐cell current through heteromeric NR1‐NR2A and NR1‐NR2B subunit combinations of NMDA channels transiently expressed in human embryonic kidney cells (HEK 293) were studied using the patch‐clamp technique. 2. With 4 mM Mg‐ATP in the internal pipette solution, the responses of cells expressing NR1‐NR2A channels to glutamate application gradually decreased, reaching 50% of control during the first 20 min of recording. This process was accompanied by acceleration of desensitization. 3. Conditioning (5‐15 s) applications of glutamate (100 microM) induced a transient inactivation of NR1‐NR2A and NR1‐NR2B channels (20‐40%) with a slow time course of recovery (tau r = 10‐60 s). Both the degree of inactivation and the time constant of recovery increased with the duration of conditioning applications of glutamate, and with an elevation of Ca2+ in the external solution. 4. These results show that both NR1‐NR2A and NR1‐NR2B recombinant NMDA receptor‐channels expressed in HEK 293 cells can be transiently inhibited by Ca2+ ions in a similar way to that described for hippocampal neurones.