The pharmacokinetics of methylphenobarbitone and phenobarbitone were studied following the administration of methylphenobarbitone on a chronic basis in 77 patients, and after a single dose to each of 4 subjects who had received no other drugs and 4 subjects who had been pretreated with various anticonvulsants and other agents. At steady-state, plasma phenobarbitone concentrations correlated better with methylphenobarbitone dose than did plasma methylphenobarbitone concentrations. In this group the ratio of plasma phenobarbitone level to plasma methylphenobarbitone level was in the range of 7 to 10:1. In the single dose studies, mean values of elimination rate constant (0.0155h) and clearance (1.85L/h) for untreated subjects were different from those for the pretreated subjects (0.0375h and 5.10L/h), while the apparent volumes of distribution did not differ significantly between the two groups (120.3L vs 140.8L). The data are interpreted as most probably indicating induction of hepatic microsomal enzymes in the pretreated group.