The pharmacokinetics of a single 300-mg oral and intravenous and 14 daily 300-mg oral doses of phenytoin were studied in 6 healthy volunteers. The mean plasma elimination t½ was the same following intravenous (16.8 ± 1.3 hr) and oral (17.1 ± 1.5 hr) doses ofphenytoin; however, following chronic oral administration, the t½ increased to 18.9 ± 1.5 hr (p < 0.05). The absolute bioavailability of an oral dosage form (Dilantin Kapseals) varied from 57.7 to 85.6% when based on the relationship between the corresponding single dose areas under the curve (AUCs). When based on the comparison of the A UC for multiple oral dosing with the single iv dose area, average bioavailability was 85.9% (71.8 to 106.3). Since the variation in the bioavailability and elimination of phenytoin does not allow accurate prediction of the steady-state plasma concentration, monitoring plasma levels may be of special importance.