Abstract 1. 1. The clinical and electroencephalographic changes which occur during chronic secobarbital intoxication and after abrupt withdrawal of this drug were studied experimentally in two groups of former narcotic addicts without previous histories of epilepsy or psychosis: group I, consisting of 14 individuals receiving 0.9 to 2.6 g. daily in divided doses for 33–89 days, and group II, including 21 individuals receiving 0.6 to 0.8 g. of the same drug daily for 38–58 days. 2. 2. During the period of chronic intoxication, the subjects in group I displayed varying degrees of ataxia, dysarthria and other changes resembling those of cerebellar dysfunction, as well as marked changes in affect, sensorium and judgment. Concomitantly, electroencephalograms were characterized by mixed rhythmic fast and slow abnormalities, mainly in frontal and parietal tracings. Tolerance developed to the clinical effects of barbiturates, but not to the electroencephalographic effects. After abrupt withdrawal of barbiturates, varying degrees of anxiety, tremulousness, postural faintness, anorexia, insomnia, and weight loss developed in almost all the subjects. In addition, 79 per cent exhibited 1–4 generalized convulsions on the second or third day of abstinence, and 65 per cent displayed psychoses, generally in the form of agitated delirium, between the 4th and 7th day of abstinence. Concomitantly, marked changes appeared in the majority of electroencephalograms, generally in the direction of periodic hypersynchronization, and with the frequent appearance of mixed spike and slow wave or 4 c/sec. “spike-and-dome” paroxysmal discharges. After the 8th day, clinical recovery proceeded uneventfully, and electroencephalograms assumed a normal pattern in the majority of cases, with only mild abnormalities in the remainder. 3. 3. During the period of chronic intoxication, the subjects in group II displayed mild or no evidence of ataxia, etc. Concomitantly, electroencephalograms were characterized by predominance of rhythmic fast activity in the frontal and parietal tracings. After abrupt withdrawal of barbiturates, abstinence phenomena were similar to but much milder than those observed in group I. Only 2 subjects exhibited, seizures, and none developed psychosis. In general, concomitant alterations in the electroencephalograms were similar to but milder than those in group I, with two striking exceptions. In these, paroxysmal discharges were more common than in any record obtained in group I. Clinical recovery proceeded uneventfully, while electroencephalograms assumed normal patterns in about half of the group, with mild random abnormalities in the remainder. 4. 4. No one-to-one correlations could be demonstrated between any given clinical state and any given electroencephalographic pattern. However, the occurrence of clinical seizures was most commonly associated with random slow, random spike, diffusely slow or paroxysmal activity in electroencephalograms, and slow abnormalities of various sorts predominated during periods of psychosis. 5. 5. The electroencephalographic changes occuring during cycles of addiction to barbiturates are discussed with reference to possible neurophysiological mechanisms.