Physostigmine is known to antagonize ketamine anesthesia. In this study, effects of physostigmine (0.1 mg kg(-1) i.p.) on ketamine (100 mg kg(-1) i.p.)-induced anesthesia time and noradrenaline release from the medial prefrontal cortex in rats were examined. Ketamine produced anesthesia for 27+/-1 min and increased noradrenaline release to 405% of the basal. Physostigmine significantly reduced anesthesia time to 23+/-1 min (p<0.05), and noradrenaline to 248% (p<0.05). Therefore, noradrenaline release may play an important role in ketamine anesthesia.