The NMDA receptor mediates excitatory neurotransmission and possesses unique functional properties, including a high calcium permeability. Calcium influx through NMDA receptors promotes neuronal survival, synaptic plasticity and, when elevated beyond homeostatic control, cell death. One process that limits calcium influx through NMDA receptors is a negative feedback mechanism known as calcium dependent inactivation (Krupp et al., 1996). Elevations in cytosolic calcium activate an array of calcium dependent proteins that negatively modulate NMDA receptors and limit calcium influx through NMDA receptor channels. This protective mechanism has not yet been studied in substantia nigra pars compacta (SNc) dopaminergic neurons: one of the key brain regions that degenerate in Parkinson’s disease. Here, we investigated the calcium dependence of NMDA receptor responses in brain slices of P7 rat SNc. Receptor inactivation was measured using whole cell patch clamp, during repeated brief (15 s) applications of 200μM NMDA at 100 s intervals. The calcium dependence of inactivation was assessed by comparing two calcium buffers in the intracellular solution: high free calcium, slow buffer (0.6mM EGTA, free calcium ~735nM) and low free calcium, fast buffer (10mM BAPTA, free calcium ~20nM). Our results show that after five NMDA applications, the decline in responses was significantly different (P<0.0005, Students t-test) in SNc dopaminergic neurones with BAPTA (45.0 ± 2.8%, n=9) compared to EGTA (65.6 ± 3.0% n=7). In non-dopaminergic neurones of substantia nigra pars reticulata (SNr), responses declined by 53.8 ± 6.7% (n=8) and 73.0 ± 3.6% (n=5) with BAPTA and EGTA respectively (P<0.05, Students t-test). In both cell types, the rate of inactivation was similar: tau = 294 s and 200 s for SNc and SNr with BAPTA and tau = 186 s and 208 s for SNc and SNr with EGTA respectively. These findings indicate a contribution of intracellular calcium to NMDA receptor modulation in the substantia nigra.