The kinetics of phenobarbital (PB) were evaluated in six normal subjects and six epileptic patients treated with phenytoin or carbamazepine. Each normal subject received three single doses of PB: PB-sodium 130 mg i.v. (IV), PB sodium 10 mg i.m. (IM), and PB acid 100 mg orally (PO), in random order at least one month apart. After IV PB distributive half-lives were 75 to 126 h, steady state volume of distribution (Vss) was 0.54 +/- 0.03 l/kg, and clearance (CL) was 3.8 +/- 0.77 ml/h/kg. Absolute bioavailability of IM PB was 101 +/- 11%. Peak serum PB concentrations were achieved from 2 to 8 h after IM administration, and from 0.5 to 4 h after PO administration. Epileptic patients exhibited similar PB kinetics: disposition half-lives were 77 to 128 h, Vss 0.61 +/- 0.05 l/kg, and Cl 3.9 +/- 0.76 ml/h/kg. Phenobarbital appears to represent an exception among antiepileptic drugs, in that pharmacokinetic data obtained in normal car reasonably be extrapolated to the epileptic population.