Objective: To compare the case fatality rate (CFR) from desipramine ingestion in children and adolescents with that of other tricyclic antidepressants. Method: All mentions of desipramine, amitriptyline, imipramine, nortriptyline, and doxepin in children and adolescents recorded in the American Association of Poison Control Centers Toxic Exposure Surveillance System from 1983 to 2002 were analyzed. The CFR for each drug was defined as the ratio of the number of deaths/number of mentioned exposures. Results: There were 24 fatalities in children younger than 6 years old (desipramine, n = 10; amitriptyline, n = 7; doxepin, n = 3; imipramine, n = 3; nortriptyline, n = 1) and 144 fatalities in older children and adolescents (desipramine, n = 56; amitriptyline, n = 30; doxepin, n = 16; imipramine, n = 31; nortriptyline, n = 11). The CFR from desipramine was significantly higher compared with the other tricyclic antidepressants in children younger than 6 years old ([chi square] = 36, p less than 0.001) and in older children and adolescents ([chi square] = 155, p less than 0.001). The CFR from desipramine exceeded that of amitriptyline, doxepin, imipramine, and nortriptyline by 7- to 8-, 4-, 6- to 12-, and 7- to 10-fold, respectively. Conclusions: The excess CFR from desipramine in children and adolescents and the reports of sudden death in children treated with therapeutic doses call for caution in prescribing desipramine to children and adolescents. (contains 2 tables.)