A number of potential Group 2 and Group 3 metabotropic glutamate receptor (mGlu receptor) agonists were investigated in adult rat brain cerebrocortical slices. The rank order of their potency in inhibiting forskolin-stimulated adenylyl cyclase was found to be: (S)-2-amino-2-methyl-4-phosphonobutyric acid (MAP4) > (2S,1'S,2'S)-2-(2-carboxycyclopropyl)glycine (L-CCG-I) > (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3S-ACPD) > (1S,3R)-1-aminocyclopentane-1, 3-dicarboxylic acid (1S,3R)-ACPD) > (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) > (S) -2-methylglutamate ((S)-MG) > L-glutamate > (2S,1'S, 2'S)-2-(2-carboxycyclopropyl)alanine (MCCG) > L-2-amino-4-phosphonobutyric acid (L-AP4) > L-serine-O-phosphate (SOP). The finding that (S)-2-amino-2-methyl-4-phosphonobutyric acid was the most potent agonist at these metabotropic glutamate receptors is in contrast to its observed potent mGlu receptor antagonist action in the neonatal rat spinal cord.