Neuropeptide Y (NPY), peptide YY (PYY), and galanin are found throughout the central nervous system with appreciable levels occurring in the striatum. In this study we have investigated the effects of these peptides on the potassium-stimulated release of endogenous neurotransmitter amino acids from slices of rat striatum. The release of glutamate was significantly reduced by nanomolar concentrations of each peptide, whilst the release of aspartate, gamma-aminobutyric acid (GABA) and glycine was not affected. The reduction in release due to galanin (200 nM) was inhibited by glibenclamide (5 muM). These results support the view that NPY, PYY and galanin modulate neurotransmitter release possibly by a presynaptic action. The results with glibenclamide suggest that the action of galanin is mediated through an ATP-sensitive potassium channel.