We determined whether enflurane-induced opisthotonus in ddN mice is mediated by N-methyl-D-aspartate (NMDA) receptor using NMDA receptor antagonists dizocilpine (MK-801) and ketamine. Animals were given intraperitoneal injections of 0.2 ml saline (control), 2.5 or 5.0 mg.kg(-1) dizocilpine in saline, or 20 or 40 mg.kg(-1) ketamine is saline 20 min prior to exposure to 2.0% enflurane. Incidence of opisthotonus measured during exposure to enflurane for 20 min was 49% (n = 51) in saline (control) group, 6.7 (P < 0.01 vs control, n = 30) and 15.0% (P < 0.01, n = 40) in 2.5 and 5.0 mg.kg(-1) dizocilpine group, respectively, and 43.9 (NS, n = 41) and 40.0% (NS, n = 40) in 20 and 40 mg.kg(-1) ketamine group, respectively. These results strongly suggest that enflurane-induced opisthotonus is mediated by NMDA receptor. Ketamine failed to suppress significantly due to possibly small dosages. Further, dizocilpine itself produced severe seizures during preenflurane period (30.0 and 40.0% in 2.5 and 5.0 mg.kg(-1), respectively), which may be a novel finding.