Tricyclic antidepressants (TCAs) have been occasionally reported to cause delirium, probably via a central antimuscarinic action. Nine of 16 patients with plasma TCA levels greater than 450 ng/ ml developed cognitive or behavioral toxicity, compared with only one of 15 patients in a control group with plasma TCA levels between 150 and 450 ng/ml. The clinician should be aware of this potential adverse effect of TCA therapy, which may be easily preventable through the combination of careful clinical monitoring and liberal use of plasma TCA levels.