The effects exerted by some anti-epileptic drugs on gross behaviour, electrocorticogram, brain acetylcholine content and cortical acetylcholine release have been investigated in normal and epileptic guinea-pigs. Focal epilepsy was provoked by heating the eserinized solution contained in an epidural cup placed on the parietal cortex. In normal guinea-pigs di- n-propylacetic acid, di- n-propylacetamide and diazepam caused sedation, synchronized the ECoG, increased the acetylcholine content in the forebrain and decreased its cortical outflow. In contrast, trimethadione and diphenylhydantoin (DPH) were ineffective in normal animals but in epileptic guinea-pigs they suppressed the convulsive symptoms and reduced the abnormally high cortical acetylcholine outflow. This finding supports the idea that specific anti-epileptic drugs, like trimethadione and DPH, influence the physiological disposition of acetylcholine only indirectly, by restraining the paroxysmal neuronal activity.