The hypothesis that electroconvulsive shock (ECS) causes disinhibition and decrement in retention by altering the activity of cholinergic neurons was investigated. In the first study rats were given a series of 4 ECS treatments in a 20-min period. One group was sacrificed immediately, another group after 4 hr, another group after 24 hr, and a fourth group after 96 hr. Acetylcholinesterase (AChE) activity for the whole brains was determined for these groups and a control group. ECS increases AChE levels which return to pre-ECS level within 96 hr. A second study attempted to eliminate or augment the retention deficit caused by ECS through the use of scopolamine (anticholinergic) and eserine (anticholinesterase). Results indicate that scopolamine partially eliminates the decrement in retention while eserine in association with ECS creates an even greater decrement. © 1969.