A 64-year-old woman with major depression developed toxic symptoms while on a regimen of 150 to 200 mg/day of desipramine. Her elimination half-life for desipramine was found to be greatly prolonged, at approximately 150 hours. Her ability to metabolize diphenhydramine and lorazepam was found to be impaired as well. Study of the elimination kinetics of desipramine in three of the patient's sisters provided some support for the existence of a genetically determined metabolic defect. Knowledge of those idiosyncratic pharmacokinetics had important implications for diagnosis and treatment in this case.