Electrophysiological and microfluorimetric measurements were combined to correlate the changes in intracellular calcium concentration to synaptic plasticity in striatal medium spiny projection neurons, during three different protocols of synaptic stimulation (1, 10, and 100 Hz). The 1 Hz stimulation protocol did not cause significant changes either in excitatory postsynaptic potential amplitude or in intracellular calcium concentration. The 10 Hz stimulation protocol induced a moderate increase of intracellular calcium without significantly affecting the excitatory postsynaptic potential amplitude. During the high frequency stimulation large, transient intracellular calcium elevations were recorded, and a significant long-term depression of excitatory postsynaptic potential was achieved. These results suggest that the induction of long-term depression required large, transient increases in intracellular calcium concentration.