The mechanism by which dopamine (DA) decreases the amplitude of the EPSP-IPSP sequences evoked by cortical stimulation was investigated by means of electrophysiological and biochemical methods. Intracellular recordings indicate that DA decreases the amplitude of the excitatory and inhibitory events by reducing the increase in membrane conductance measured at the peaks of the EPSP-IPSP. The non-synaptic input resistance was not modified. In addition the catecholamine (+50/+200 nA balanced current) was shown to decrease the action of glutamate (-30/-80 nA balanced current) and GABA (+40/+100 nA balanced current) when iontophoretically applied. These observations suggest that DA interferes with the excitatory (glutamatergic) and inhibitory (GABAergic) transmission at the postsynaptic site in striatal neurons. However, the depression of cellular excitability elicited by DA could not be ascribed only to its interaction with synaptic transmission at the postsynaptic level. In fact the catecholamine also inhibited spike frequency driven by depolarizing pulses and decreased the depolarization-induced release of glutamate at the presynaptic site, as shown by biochemical experiments with striatal synaptosomal preparations. A neuromodulatory role of DA in the depression of the excitability of striatal neurons by presynaptic and postsynaptic mechanisms is suggested.