The concept that phenobarbital sodium interferes with metabolism of griseofulvin due to its ability to induce liver enzymes that increase drug metabolism was tested by a random crossover study of six healthy male volunteers who received griseofulvin orally and intravenously, both with and without phenobarbital. The elimination kinetics of griseofulvin for a given subject were identical with or without the administration of phenobarbital; thus, no evidence for enzyme induction was observed. However, the amount of orally administered griseofulvin absorbed with phenobarbital administration fell well below that seen when no phenobarbital was given, implying that phenobarbital reduces absorption of the drug.