The pharmacokinetics and bioavailability of mephobarbital have been studied in 2 volunteers. Plasma levels of mephobarbital and phenobarbital were measured by gas chromatography-mass spectroscopy with selected ion monitoring. Urinary output of phenobarbital and the p-hydroxy derivatives of both mephobarbital and phenobarbital was measured by high pressure liquid chromatography. The time course of these plasma and urinary levels was monitored following single 800-mg oral and 200-mg intravenous doses in the 2 patients. The major conclusions of the study were that mephobarbital is reasonably well absorbed following oral dosing and that some 35% or so of the dose (by either route) is converted to the recently identified metabolite, p-hydroxymephobarbital.