The effects of diphenylhydantoin [phenytoin (PHT)] on both the acute withdrawal syndrome (AWS) and the asthenic-autonomic syndrome associated with chronic alcoholism were evaluated in a single-blind, controlled, clinical, and comprehensive multiparameter psychophysiological and neurophysiological study. Twenty-four patients were treated with PHT (100 mg, PO, tid) and our standard detoxification therapy (intravenous fluids and vitamins as an antihistamine and a vasodilator; cognitive psychotherapy; and occupational therapy) and their progress was compared to that of 12 patients receiving only our standard detoxification therapy. The use of PHT and standard detoxification therapy resulted in an amelioration or cessation of the main symptoms of acute alcohol withdrawal within a mean of 3 +/- 1 days. Vital fear, psychomotor excitation, sense of shortness of breath, pronounced chill-like state, and pronounced perspiration disappeared within 3 days. In the control group, the same improvements were found in a mean of 11 +/- 3 days. After the acute withdrawal period, PHT (50-100 mg, bid-tid) was continued in all 24 patients of the PHT group to evaluate its effects on the asthenic-autonomic syndrome. PHT's most marked therapeutic effects (improvements in mood, aggression, ability to react appropriately to surroundings, attention, active vigilance, and autonomic parameters) were seen in eight patients with the sympathetic-adrenal type of autonomic disorders. Dynamic EEG and infraslow physiological processes showed confirmatory improvement. A reduction in alcohol craving and longer alcohol-free remission times were also seen. Although there were some benefits in the 16 patients with the parasympathetic type of autonomic disorders, they were smaller and less stable. There were no beneficial effects of PHT or standard therapy in a group of five young patients with a malignant, rapidly progressive form of alcoholism. We conclude that PHT is useful in acute alcohol withdrawal and in the treatment of the asthenic-autonomic syndrome (during the rehabilitative phase) in patients with sympathetic type of autonomic disorder. Further clinical evaluation and use of PHT in alcohol withdrawal and rehabilitation are indicated.