We have studied the electrophysiological effects of glucose deprivation on morphologically identified striatal neurons recorded from a corticostriatal slice preparation. The large majority of the recorded cells were spiny neurons and responded to aglycemia with a slow membrane depolarization coupled with a reduction of the input resistance. In voltage-clamp experiments aglycemia caused an inward current. This current was associated with a conductance increase and reversed at -40 mV. The aglycemia-induced membrane depolarization was not affected by tetrodotoxin (TTX) or 6-cyano-7-nitroquinoxaline-2,3-dione plus aminophosphonovalerate, antagonists acting respectively on AMPA and NMDA glutamate receptors. Also, the intracellular injection of bis(2-aminophenoxy)ethane-N,N, N',N'-tetra-acetic acid, a calcium (Ca2+) chelator, and low Ca2+/high Mg2+-containing solutions failed to reduce this phenomenon. Conversely, it was reduced by lowering external sodium (Na+) concentration. A minority of the recorded cells had the morphological characteristics of large aspiny interneurons and the electrophysiological properties of "long-lasting afterhyperpolarization (LA) cells." These cells responded to aglycemia with a membrane hyperpolarization/outward current that was coupled with an increased conductance. This current was not altered by TTX, blockers of ATP-dependent potassium (K+) channels, and adenosine A1 receptor antagonists, whereas it was reduced by solutions containing low Ca2+/high Mg2+. This current reversed at -105 mV and was blocked by barium, suggesting the involvement of a K+ conductance. We suggest that the opposite membrane responses of striatal neuronal subtypes to glucose deprivation might account for their differential neuronal vulnerability to aglycemia and ischemia.