Using microdialysis, we examined the effects of ketamine and pentobarbitone on acetylcholine (ACh) release from the rat hippocampus and striatum. Ketamine 25 and 50 mg kg(-1) increased ACh release from the hippocampus to 295% and 353% of basal release, respectively, but not from the striatum. SCH 23390 1 mu mol litre(-1), a D1 antagonist, significantly inhibited the facilitatory effect of ketamine 50 mg kg(-1) on hippocampal ACh release (to 241% of basal level). In contrast, pentobarbitone 20 and 40 mu mg kg(-1) decreased basal ACh release from both the hippocampus by 41% and 69%, respectively, and the striatum by 37% and 58%, respectively. The results suggest that ketamine and pentobarbitone exert opposite effects on ACh release from the rat hippocampus and that the stimulating effect of ketamine may involve dopamine D1 receptors.