We report for patients with encephalitis treated with plasma exchange (PE) and fosphenytoin. In patient 1, phenytoin levels decreased on the maintenance dose, and the phenytoin concentration was <10 μg/mL on day 12 of administration. In patient 2, the phenytoin levels was <10 μg/mL on day 4. Increasing the fosphenytoin dose pushed the phenytoin level into therapeutic range. There were no differences between the areas under the concentration-time curve of phenytoin with and without PE. We previously reported a decline in phenytoin levels after prolonged use of fosphenytoin. Therefore, dose adjustment of fosphenytoin in patients undergoing PE may be unnecessary.