Learning deficits resulting from dopamine depletion suggest that striatal dopamine release is crucial for reinforcement. Recently described firing patterns of dopamine neurons in behaving monkeys show that transient increases in dopamine release are brought about by reinforcement. We describe an enduring change in the strength of synaptic transmission following pulsatile application of dopamine intended to mimic the transient increases associated with reinforcement. Intracellular records were made from neurons in slices of the rat corticostriatal system. Neurons having the properties of the medium-sized spiny neurons responded to cortical stimulation with depolarizing potentials (peak amplitude 12.0 +/- 1.3 mV; latency 9.2 +/- 0.1 ms; mean +/- S.D., n = 19), which had the properties of monosynaptic excitatory postsynaptic potentials. After trains of stimuli to the cortex had been applied in conjunction with intracellular depolarizing current, the size of these excitatory postsynaptic potentials was reduced (-27% at 20 min). Application of dopamine (approximately 30 microM) in a solution containing KCl concomitant with depolarization and presynaptic activation increased the subsequent excitatory postsynaptic potentials (+21% at 20 min) without significant lasting change in the membrane properties of the postsynaptic cell. This suggests that dopamine has an enduring, activity-dependent action on the efficacy of corticostriatal transmission, which may be a cellular basis for the learning-related effects of the nigrostriatal system.