Levels of diphenylhydantoin sodium in the blood can be correlated with its clinical effects and intoxication. Therapeutic levels (10μg/ml to 15μg/ml are reached within 5 to 15 days when 300 mg are given daily; and with a larger (up to 1,000 mg) initial dose, within a few hours (orally) or minutes (intravenously). Two groups of unusual responses to commonly used doses of diphenylhydantoin have been observed. (1) Low tolerance to the drug which can be caused by congenital enzymatic deficiency, liver disease, or metabolic interference by other drugs. A reduction of the daily dose is necessary in these patients. (2) Refractoriness to diphenylhydantoin which can be caused by excessive diphenylhydantoin metabolism, deficient absorption, and unreliable diphenylhydantoin intake. An increase of dose, administering diphenylhydantoin parenterally, or supervising drug intake will provide adequate blood levels in these patients.