The corticotropin-releasing factor (CRF) is a hypothalamic peptide that regulates the release of adrenocorticotropic hormone (ATCH) and of beta-endorphin. It has been suggested that it modulates learning and memory processes in rat. However, the electrophysiological effects that CRF produces on hippocampal neurons have been so far little investigated. In particular, the effects of CRF on long-term potentiation (LTP), a phenomenon which is thought to be the substrate of memory processes, are unknown. We studied the effects of sustained administration of CRF and of two of its receptor agonists on basal neuronal activity and on in vitro hippocampal LTP. The two receptor agonists were D-Glu-20-CRF and D-Pro-5-CRF, selective for the CRF-R1 and the CRF-R2 receptors, respectively. We found that CRF, D-Pro-5-CRF and D-Glu-20-CRF at the concentration of 1 nM diminish the amplitude of hippocampal population spike and prevent the onset of LTP. Higher concentrations of CFR have less depressing effects on neuronal activity, yet they still prevent the occurrence of LTP.