The effects of intracerebral administration of L-kynurenine (L-KYN) on the N-methyl-D-aspartate (NMDA) receptor-mediated, nitric oxide (NO)-dependent cGMP responses have been studied in vivo in the cerebellum and hippocampus of freely-moving rats subjected to transcerebral microdialysis. Administration of exogenous NMDA in the cerebellum through the dialysis probe evoked a 3-fold increase of basal extracellular levels of cGMP that was concentration-dependently reduced by co-infusion of L-KYN. In the hippocampus, local administration of cyclothiazide caused a significant enhancement of the cyclic nucleotide dialysate concentrations that was accompanied by behavioural manifestations characteristic of preconvulsive states. Co-infusion of L-KYN largely decreased the neurochemical effects of cyclothiazide and completely prevented the appearance of the behavioural episodes. It is concluded that administration of L-KYN by increasing endogenous kynurenic acid concentrations might exert neuroprotective and anticonvulsive effects through blockade of the NMDA receptor/NO/cGMP pathway.