1. We investigated the effects of neuropeptide Y (NPY), peptide YY (PYY), NPY13-36, NPY18-36, [Leu31][Pro34]NPY and of pancreatic polypeptide Y (PPY) on calcium-dependent, potassium-stimulated glutamate release in superfused rat hippocampal slices. 2. NPY, PYY and the Y2 receptor agonist NPY13-36 equipotently inhibited the release of glutamate. The half-maximal response was observed at about 10 nM in a dose-dependent manner (3 to 100 nM). Maximal inhibition of 50 to 60% was obtained at 100 nM. At higher concentrations of the peptides (300 nM and 1 microM) this inhibition was partially or entirely reversed. Porcine NPY13-36 and NPY18-36 inhibited glutamate release by about 44% at 100 nM. 3. The specific Y1 receptor agonist, [Leu31][Pro34]NPY, caused an insignificant increase in glutamate release at 100 to 300 nM concentrations. PPY had no effect on potassium-evoked glutamate release in hippocampal slices at concentrations of 30 nM to 1 microM. 4. The experiments support previous electrophysiological data. They suggest a potent inhibitory action of NPY through NPY-Y2 receptors on the release of the excitatory amino acid glutamate in rat hippocampus. Especially under conditions of increased NPY synthesis, such as in epilepsy, this mechanism may be of pathophysiological relevance.