1. The study was designed to determine the mechanism by which vigabatrin causes a fall in plasma phenytoin concentrations when added to the drug therapy of eight epileptic patients. 2. Total plasma phenytoin concentration was measured before and at intervals during 5 weeks' treatment with vigabatrin. 3. Plasma protein binding of phenytoin, the urinary ratio of phenytoin to 5-(p-hydroxyphenyl)-5-phenylhydantoin, and antipyrine clearance were measured before and at the end of treatment period. 4. Mean plasma phenytoin concentration fell significantly by 23% during the fifth week. 5. No change was found in any of the other measures. 6. Although an interaction between phenytoin and vigabatrin has been confirmed, the mechanism has not been elucidated.