The effects of acute and repeated treatment with 1-(2-pyrimidinyl)piperazine (1-PP), a metabolite of the 5-HT1A receptor ligand azapirones, were investigated on hippocampal excitatory synaptic transmission. Recordings of the electrically evoked field population excitatory post-synaptic potentials (e.p.s.p.s.) were carried out in the stratum radiatum of the CA1 region of the dorsal hippocampus of alert rats. Acute i.p. administration of 1-PP transiently reduced the e.p.s.p. amplitude in a dose-dependent (0.25-1 mg/kg) manner. This effect was blocked by the 5-HT1A receptor antagonists spiroxatrine (1 mg/kg) and MDL 73005EF (8-[2-(2,3-dihydro-1,4-benzodioxin-2-yl methylaminoethyl]-8-azaspirol[4,5]decane-7,9-dione methyl sulphonate, 2 mg/kg). Intrahippocampal administration of 1-PP (5 microg) evoked a transient reduction of the e.p.s.p. amplitude which was similar to that obtained with 5-HT (10 microg). 1-PP (0.25 mg/kg per day) administered for 9 days produced a gradual reduction in the daily pre-injection baseline e.p.s.p. amplitude coupled with a decrease in the acute response to the drug. The chronic baseline reduction was transiently reversed by spiroxatrine and full recovery to pretreatment levels was observed 4 days after the last 1-PP dose. These findings indicate that the previously reported reduction in the e.p.s.p. produced by the azapirone group of 5-HT1A receptor ligands may be mediated in part by their metabolite 1-PP through activation of 5-HT1A receptors.