Since the influence of the autonomic nervous system on epileptic phenomena became the subject of intensive investigations, several contradictory reports have been published. Williams and Russell (1941) and Williams (1941) found that parasympathetic overactivity (induced chemically and registered by electro-encephalography) increases epileptic activity. Darrow (1944) reported opposite results, his observations being based on electrically induced parasympathetic overactivity on animals. He registered his observations by electroencephalography. Cohen, Thale and Tissenbaum (1044) induced convulsions for therapeutical purposes by administering the parasympathomimetic drug, acetylcholine, and Chatfield and Dempsey (1942) observed the production of fits in cats, when giving acetylcholine and prostigmine together. Though the results were contradictory, the main aim of all these investigations was to establish the cholinergic neurohumoral changes in relation to epilepsy. But, as Williams pointed out, it is impossible to say whether the results are due to a direct central action, are consequent upon changes in the pH or of a respiratory or a circulatory nature. The investigations described in this paper were devised to re-examine these problems clinically. They were based on the hypothesis that if cholinergic overactivity enhances epileptic cerebral activity, the convulsive threshold of the brain should be lowered after administration of anticholinesterases, in particular prostigmine.