The authors report a case of bupropion-associated delirium characterized by disorganized thinking, memory impairment, fear, and agitation but not disorientation, delusions, hallucinations, or other perceptual distortions. Symptom onset appeared to be dose-related, and a sustained therapeutic response was subsequently obtained at a lower dose of bupropion without recurrence of delirium. Abnormal bupropion metabolism and elevated plasma metabolite levels did not account for the adverse reaction, which instead was hypothesized to reflect dopaminergic effects of bupropion.