Mirtazapine is the first of a new class of antidepressants, the noradrenergic and specific serotonergic antidepressants. Its antidepressant effect appears to be related to its dual enhancement of both noradrenergic neurotransmission and serotonin 5-HT1 receptor-mediated serotonergic neurotransmission. Mirtazapine has demonstrated superior tolerability to the tricyclic antidepressants, primarily on account of its relative absence of anticholinergic, adrenergic and serotonin-related adverse effects. We observed mirtazapine-induced delirium in one organically depressed and two major depressed patients with subclinical brain disease. The appearance of hallucinations, psychomotoric agitation and cognitive changes after initiation of mirtazapine, and their prompt improvement after drug discontinuation, led to the impression that these were drug-induced phenomena. One possible hypothesis for the observed deliria is a central increase of norepinephrine after acute administration of mirtazapine. Subclinical brain disease might have favoured the occurrence of delirium in the three cases.