A striatal synaptosomal preparation was used to assess the action of metabotropic glutamate receptor (mGlu receptor) agonists on 4-aminopyridine (2 mM)-stimulated endogenous glutamate release. 4-Aminopyridine alone increased basal glutamate release by 6.89 ± 0.74 nmol/mg. The mGlu receptor agonists l-2-amino-4-phosphonobutyric acid (l-AP4) (IC 5 0 0.2 μM) and (1S,3S)-1-amino-cyclopentane-1,3-dicarboxylic acid (IC 5 0 0.2 μM) inhibited 4-aminopyridine-stimulated release. The putative mGlu receptor antagonist (S)- -methyl-l-AP4, which itself inhibited 4-aminopyridine-stimulated release (IC 5 0 10 μM), did not inhibit the effects of the two agonists.