Effects of repetitive dextromethorphan at adolescence on a spatial learning of rats were investigated. Rats received 10 daily injections of dextromethorphan (40 mg/kg) from postnatal day 28 thru 37, and were then subjected to the Morris water maze task from day 38. Significant impairments were found in the probe trial and the reversal training of the maze learning in the female rats, but not in males, treated with dextromethorphan. This result suggests that repetitive dextromethorphan, that is, abuse of dextromethorphan, at adolescence may induce deficits in the hippocampus-based memory function, perhaps more obviously in females.