The sudden collapse and death in three prepubertal children during routine treatment with desipramine was recently reported in brief statements. Insufficient clinical information is available to infer a cause-and-effect relationship between the therapeutic use of desipramine and sudden death in these children. Speculatively, a variety of possible mechanisms could account for sudden death in children receiving treatment with tricyclic antidepressants: a cardiac event, an increase or decrease in blood pressure, an increase in pulse, a seizure (with complications), or heat stroke. The extent of medical monitoring in the three cases is not clear, leaving unresolved whether a change in standard monitoring procedures is indicated. The total number of children who have received desipramine treatment is not known, so it is not possible to specify the incidence of this putative adverse effect. It is clear that the incidence of death from accidental overdose is substantially higher. Given the current available level of knowledge about these cases, no clinical recommendations are offered concerning when to avoid or to use desipramine; however, certain clinical considerations regarding the use of antidepressants in children are raised and discussed.