Single, 50- and 100-mg oral doses of phenobarbital and a matching placebo were administered double-blind to 8 young, healthy male subjects. Multilead electroencephalographic (EEG) samples were recorded prior to, and at regular intervals within the 2 h following administration. The EEG signal was processed by power spectral analysis; the drug plasma concentration was assessed concomitantly. Plasma peaks after the 50- and 100-mg dose were, respectively, 3.38 ± 1.29 and 4.09 ± 1.24 μg/ml. Despite the low drug plasma concentration, a systematic power increment of the EEG fast frequency spectral segments occurred at either dose on the anterior scalp areas from the 30- or 60-min postdrug control onward, and was preponderant on central electrodes; a significant correlation (Kendal’s coefficient for ranked data) with the drug plasma concentration was observed limitedly to the anterior scalp areas. No correlation with plasma levels was observed for unsystematic EEG variations.