Striatal slices, preincubated with [3H]dopamine and [14C]choline, were superfused continuously and subjected to electrical field stimulation (3 Hz) and perfused with amino acid analogues or 4-amino pyridine (4-AP). The released radioactivity was used to monitor release of the neurotransmitters dopamine (DA) and acetylcholine (ACh). Glutamate, NMDA (in the absence of Mg2+), AMPA, kainic acid, domoate and 4-AP all induced DA and ACh release in a concentration-dependent manner. The DA and ACh release induced by NMDA (15 microM) and glutamate (1 mM) was essentially abolished by Mg2+ (1.15 mM), whereas release induced by AMPA (100 microM), kainic acid (100 microM) or 4-AP (30 microM) was not reduced. Tetrodotoxin (1 microM) essentially abolished the effects of NMDA, markedly reduced the effects of glutamate, AMPA and 4-AP, whereas the effect of kainic acid was only modestly affected. MK-801 (30 nM) reduced NMDA-induced DA release by some 70% and ACh release by 30%. MK-801 reduced 4-AP-induced DA release by 40% but not ACh release. CNQX in a concentration (10 microM) that scarcely affected NMDA-induced ACh release, but blocked that induced by AMPA, kainic acid or domoate, reduced the ACh release induced by 4-AP. In summary, DA and ACh release from rat striatum can be stimulated by activation of NMDA and non-NMDA glutamate receptors, and this mechanism is activated by the potassium channel blocker 4-AP.