Angiotensin-converting enzyme (ACE) inhibitor has mood-elevating effects, and central ACE activity is increased for suicidal patients. In addition, substance P (SP), which is degraded by ACE, has been implicated in the pathogenesis of, and evaluated in the treatment for, major depressive disorder (MDD). The present study has tested the hypothesis that an ACE-gene insertion/deletion (I/D) polymorphism is associated with onset age, clinical manifestations, suicide history, and/or antidepressant response for two groups of MDD patients. No significant differences were demonstrated for onset age (p = 0.520), suicide history (p = 0.823), or baseline, total and cluster scores for Hamilton Depression Rating Scale comparing the three ACE genotypes. Further, previous findings that this ACE polymorphism is associated with therapeutic antidepressant effects were not replicated. The results demonstrate that these ACE variants did not play a major role in the clinical manifestations or antidepressant response for our MDD patients.