Plasma levels of diphenylhydantoin have been measured in 130 epileptic patients undergoing long-term anticonvulsant therapy. Only in a small percentage of the patients (15,38%) plasma levels were found to lie within the therapeutic range. Most patients (75,38%) exhibited subtherapeutic values, while in a few cases (9,24%) the upper limit of therapeutic range was exceeded. Although plasma concentrations significantly correlate with the administered dose, predictability of plasma levels in the individual patients given fixed dosage schedules is strongly limited by large interindividual variability. Sex, age and simultaneous administration of other drugs seem not to affect significantly DPH plasma levels. Our observations carried out in a meaningful sample of epileptic patients suggest that at present the practice of monitoring diphenylhydantoin plasma levels is still an essential tool for the management of epilepsy when a safe and effective therapeutic regimen is required.