We evaluated the therapeutic effects of remacemide hydrochloride, an N-methyl-D-aspartate (NMDA) receptor-associated ionophore blocker with sodium channel blocking activity, on cortical lesion volume and memory dysfunction following parasagittal fluid-percussion brain injury in the anesthetized rat. We found that intravenous (i.v.) administration 15 min following injury of remacemide hydrochloride at both 25 and 10 mg/kg significantly reduced posttraumatic cortical lesion volume (P < 0.05), measured at 48 h postinjury using a tetrazolium salt tissue staining technique. However, neither of these doses nor the dosing regimen of 25 mg/kg i.v. 15 min postinjury plus a subcutaneous infusion over 24 h of 20 mg/kg remacemide hydrochloride improved posttraumatic memory function determined by a Morris water maze paradigm.