BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA) is one kind of amphetamine-type stimulants (ATS) with stimulating and hallucinogenic properties, and its damage to human is extremely serious and complicated. It has become a research hot in the field of addiction behavior abroad. OBJECTIVE: To observe the effect of long-term neurotoxicity of MDMA on cognitive function. DESIGN: A randomized control animal experiment. SETTING: Laboratory of Psychopharmacology, Mental Health Center, West China Hospital of Sichuan University. MATERIALS: The experiment was carried out in the Laboratory of Psychopharmacology of the Mental Health Center, West China Hospital of Sichuan University from July 2003 to February 2004. Sixteen male adult Wistar rats, provided by the animal center of Sichuan university, were randomly assigned to study group (n=10) and control group (n= 6). INTERVENTIONS: Rats in study group were administrated with MDMA (10 mg/kg), once per hour for four times, and the total amount was 40 mg/kg, and those in the control group were treated with saline of the same volume. The Morris water-maze test was performed at 2, 8, 26 and 32 weeks after the last administration respectively to observe the spatial learning and memory function. MAIN OUTCOME MEASURES: The escape latencies and the times of crossing the exact position of the former platform were observed at 2, 8, 26 and 32 weeks after the last administration respectively. RESULTS: Four rats in the study group died within 12 hours during the experiment, 1 in the study group and 1 in the control group died at 6 and 17 weeks respectively, finally 5 rats in the study group and control group left till 32 weeks respectively. At 2, 8, 26 and 32 weeks after the last administration, there were no .significant differences in the escape latencies between the two group (P ＞ 0.05), and the times of crossing the exact position of the former platform also had no significant differences [(7.67±2.16), (7.50±2.95) times; (6.60±1.14), (7.0±1.67) times;(7.40±1.52), (6.60±2.61) times; (6.80±4.55), (5.80±1.79) times; P ＞ 0.05]. CONCLUSION: The long-term neurotoxicity of MDMA has no obvious effect on the spatial learning and memory function.