Activation of NMDA receptors in substantia nigra pars compacta (SNc) dopaminergic neurones induces a voltage-dependent burst firing (Johnson et al. 1992) that regulates dopamine release in the striatum. The voltage dependence of magnesium block of NMDA receptors is a critical determinant of their normal physiological role. In SNc, NMDA receptors may be triheteromers of NR1, NR2B and NR2D subunits (Jones & Gibb, 2005) and thus could have an unusual voltage dependence. We have used patch-clamp whole-cell recording methods to quantify magnesium block of NMDA receptors in 300 μm thick coronal slices of SNc from 7 day old rats. Responses to 0.01 mM NMDA and 0.01 mM glycine in the presence of TTX (100 nM) with 3mM ATP and 1mM GTP in the pipette solution were recorded and the voltage dependence of the net whole-cell NMDA current evoked during voltage ramps (-100 mV to +40 mV of 2 s duration) in the absence of magnesium, and in the presence of 0.1 mM or 1.0 mM magnesium quantified using a model that included the possibility of magnesium block of the NMDAR channel from both outside and inside as well as binding of magnesium to a voltage-independent potentiation site on the extracellular site of NR2B subunit-containing receptors (Paoletti et al. 1997). Of the tested neurons 85% showed a hyperpolarisation-activated slow inward current (Ih current) characteristic of dopaminergic cells and in these cells at -60 mV, 0.1 mM magnesium blocked the NMDA current by 35.3–72.5% while 1.0 mM magnesium blocked the NMDA current by 83.7–93.5% (n = 6 cells). Using the current-voltage relation from these cells we estimate the fraction (delta) of the membrane field sensed by magnesium at it’s binding site to be 0.54 and the dissociation equilibrium constant for binding at 0 mV (Kb(0mV)) to be 1.3 mM. These results suggest that the voltagedependence of magnesium block of NMDA receptors in SNc cells is more similar to that observed for NR2C or NR2D subunit-containing NMDA receptors than for NR2A or NR2B receptors.