The effects of systemic administration of strychnine (1 mg/kg), picrotoxin (0.5 mg/kg) and bicuculline (2 mg/kg) on acute transsynaptic destruction of medullary dorsal horn neurons following transection of the inferior alveolar nerve were assessed in rats. Single intraperitoneal injections of the above drugs were given without, 1 min before or 1 min after the nerve transection. The effect of transection without drug administration was also examined. Eighteen hours after nerve transection without drug, approximately 7 dark neurons were found in a single toluidine blue stained 1 micron section of the rostral medullary dorsal horn ipsilateral to the nerve transection. Administration of the drugs 1 min before the nerve transection significantly increased the number of dark neurons in a single section to about 17 (strychnine), 46 (picrotoxin) and 20 (bicuculline). These dark neurons were found mainly in the dorsal half of medullary dorsal horn. Delivery of any of the drugs 1 min after the nerve transection did not increase the number of dark neurons. The data thus indicate that the transneuronal effect of transection of the nerve was enhanced by antagonism of glycinergic and GABAergic inhibition of dorsal horn neurons. In view of the short latency and duration of transsynaptic destructive activity, a massive injury discharge of primary afferent neurons and the subsequent release of excitatory neurotransmitters appear to be the direct cause of convulsant-enhanced rapid transsynaptic destruction which follows the peripheral nerve transection.