1. In the present study we investigate the expression of a persistent Na+ conductance (INaP) in identified medium-sized neostriatal neurons. Nomarski optics and infrared videomicroscopy were used for cell visualization and identification in thick slices (350 microns). Current- and voltage-clamp recordings were obtained utilizing whole cell patch-clamp methodology. 2. Application of depolarizing ramp voltage commands from a holding potential of -70 mV induced a slow, noninactivating inward current that occurred before and independent of the rapidly inactivating sodium current that subserves action potential generation. INaP began to activate at potentials less negative than -70 mV and peaked at -34 +/- 1 (SE) mV. Its average peak amplitude was -100 +/- 17 pA. INaP was abolished by tetrodotoxin (TTX, 0.5-1 microM) or an Na(+)-free solution. In contrast, it was not affected by Ca2+ channel blockers. Depolarizing ramp commands also induced tetraethylammonium-sensitive outward currents. 3. Dopamine (DA) (20-100 microM) produced a significant reduction of INaP. 4. These results demonstrate the existence of a TTX-sensitive persistent Na+ conductance in medium-sized neostriatal neurons. This conductance is modulated by DA and could play a role in the generation of rhythmic oscillations and in supporting repetitive firing.