Depression has been consistently reported in 40-50% of suicides. Previous toxicologic studies of suicides have not included diagnostic information, however. This report includes 247 (87%) of 283 suicides in whom it was possible to perform toxicological analyses for tricyclic antidepressants. We wanted to see if any relationships existed among the presence of antidepressants at autopsy, diagnosis of Depression, recent contact with physicians and prescription of antidepressant medication. Toxicology was positive in 19 (8%) subjects. Only 12% of the subjects with a DSM-III diagnosis of Major or Atypical Depression were positive. Lethal blood levels of antidepressants were found in only 4% of all subjects and most of those involved multiple drugs. Also, most of those subjects had co-morbid Depression and Substance Abuse. More than half of the Depressed subjects had seen a physician within 90 days from suicide but less than half of these were prescribed antidepressants and only one-third of the latter were positive for antidepressants in toxicology. These data suggest that more suicides might be averted by decisively treating Depressed patients with ADs, including strict monitoring of dosage and compliance, than by not treating them to avoid AD overdoses. Diagnostic caution should be observed to identify co-morbid Substance Abuse when treating patients with Depression and suicidal ideation.