The authors tested the pharmacokinetic interaction between benzodiazepines and nortriptyline in five patients. Each patient was tested during periods of treatment with neuroleptics, diazepam, and chlordiazepoxide, and in a drug-free control period. Neuroleptics (haloperidol and perphenazine) caused changes indicating inhibition of metabolism of 14C-nortriptyline. Neither of the two benzodiazepines caused a significant change in the pharmacokinetic measurements of 14C-nortriptyline. In rats, the metabolism of 14C-nortriptyline was inhibited by pretreatment with chlordiazepoxide, but only when given in a dose of 60 mg./kg. a short time before the administration of 14C-nortriptyline.