The concomitant administration of pethidine (meperidine) and phenobarbitone results in enhanced sedation in a patient previously tolerant of pethidine. A complete analysis of pethidine kinetics and metabolism was performed in this patient, in four additional patients undergoing similar treatment but not receiving phenobarbitone, and in a volunteer after placebo and phentobarbitone pretreatment. The results indicate that phentobarbitone enhances the production of the toxic metabolite norpethidine by increasing N-demethylation.