The neuropeptide nociceptin/orphanin FQ (N/OFQ) is implicated in many biological functions, including nociception, locomotor activity, stress and anxiety, drinking and food-intake. N/OFQ has also been reported to play a facilitatory role in acute kainate-induced seizures. The aim of the present study was to investigate its involvement in a chronic model of temporal lobe epilepsy, kindling epileptogenesis, using N/OFQ knock-out mice and their wild-type littermates as controls. Kindling development was retarded in N/OFQ-deficient mice, in that (compared with controls) they required a significantly greater number of stimulations and a significantly longer time in electrical seizures to reach kindling criteria. These data indicate that N/OFQ is involved in the development of kindling and that it may play a pro-epileptogenic role.