Toluene abuse during pregnancy results in newborns with fetal solvent syndrome. N-Methyl-D-aspartate (NMDA) receptor has been identified as a target site for toluene. Since the normal function of NMDA receptor is critical for synaptogenesis, the long-term effects of toluene exposure during synaptogenesis on the neurobehavioral function and the expression of NMDA receptor subunits (NR1, NR2A, and NR2B) were examined. Rats exposed to l g/kg of toluene (i.p.) over postnatal days 4 to 9 were found to exhibit reduction in body weight, NMDA-induced seizure thresholds, and MK-801-induced hyperlocomotor activity. Furthermore, immunoblotting and immunohistochemical analysis revealed a significant increase in NR2A subunit expression in the hippocampus and cerebellum of toluene-exposed rats on PN30. These results suggest that the region-specific changes in the expression of NMDA receptor subunits may play a role in the neurobehavioral dysfunction following toluene exposure during synaptogenesis.