We have studied the effects of ketamine and pentobarbitone on acetylcholine (ACh) release from the rat frontal cortex using microdialysis. Ketamine 25, 50 and 100 mg kg-1 increased ACh release from the frontal cortex to 286%, 253% and 381% of basal release, respectively. In contrast, pentobarbitone 10, 20 and 40 mg kg-1 caused 73%, 78% and 96% inhibition of basal levels, respectively. The results suggest that ketamine and pentobarbitone have opposite effects on ACh release from the rat frontal cortex, as seen previously in the rat hippocampus.