Rifampin is well documented to cause numerous clinically significant drug interactions because of its induction of the hepatic cytochrome P450 system. The metabolism of nortriptyline and other tricyclic antidepressants is induced and inhibited by this enzyme system. To the authors' knowledge, this is only the second case report in the literature regarding a possible interaction between rifampin and a tricyclic antidepressant. Nortriptyline serum concentrations were not detectable while rifampin was given concurrently. Two weeks after discontinuation of rifampin, nortriptyline concentrations increased dramatically. Further study of this possible interaction is warranted.