The effect of neuropeptide Y (NPY) on the picrotoxin-induced activity was studied in rat brain hippocampal slices in vitro and after intrahippocampal injection in vivo. In the hippocampal slices, NPY (0.1-0.5 microM) inhibited the picrotoxin-induced epileptiform activity recorded extracellularly in CA1 and CA3 hippocampal pyramidal cells. Similar inhibition was induced by the Y2 receptor agonist NPY13-36, which indicates that the effect of NPY was due to activation of Y2 receptors. In behavioural studies, rats with chronically implanted cannulae were injected unilaterally into the CA1 hippocampal region with a 1 ml volume of the studied substances. Picrotoxin in a dose of 1 mg (1.6 nmol) induced behavioural excitation, shakes and weak signs of epileptic behaviour. NPY in a dose of 2 mg (470 pmol), but not 1 mg, inhibited some excitatory effects of picrotoxin, but did not change the epileptic symptoms. The obtained results suggest that NPY has an inhibitory action in the hippocampus, which can be observed in vitro and also in a behavioural study.