In the debate on euthanasia and physician-assisted suicide, we have to exclude terminally ill patients in whom the desire for death is caused by major depression. However, it is still not clear to what degree major depression can be treated by psychiatric intervention in this setting. We evaluated the effect of antidepressant treatment in terminally ill cancer patients. Six cancer patients with suicidal ideas thought to be due to major depression were treated with tricyclic antidepressants. Three had requested terminal sedation to relieve them from their suffering. The median survival of five of these patients was 4 weeks after diagnosis; one was lost to follow-up. The efficacy of the antidepressant treatment was assessed using the Hamilton Rating Scale for Depression (HRSD). One week after the start of treatment with antidepressants, five of the six patients showed a marked improvement in their mood and showed no further suicidal thoughts or requests for terminal sedation. The average reduction in the HRSD score was 23.4 points (14-38; SD = 9. 9). Antidepressant treatment can be effective in alleviating the desire for death due to major depression, even in terminally ill cancer patients.