An investigation of the ratio of free to bound phenytoin in overdose cases was accomplished by three studies to answer these questions: 1. Will the free to bound ratio change with increasing total phenytoin concentration? 2. Will the free to bound ratio be altered with decreasing total protein concentration? 3. Do these results correlate with overdose cases? The results demonstrated that the ratio of free to bound phenytoin remains constant throughout the therapeutic range as long as a person has a normal total protein concentration. However, the free to bound ratio changes significantly when the total protein decreases by 25 per cent. This substantiates the importance of monitoring free and total phenytoin concentrations in hypoproteinemia.