Purpose: Prostate cancer is the most common malignancy in men and one of the leading causes of cancer death in men internationally. Treatment for prostate cancer frequently includes androgen deprivation therapy (ADT). Reports of depressive symptoms arising during ADT are emerging. This study examines the prevalence rates and risk factors associated with major depression in this population. Method: 45 men with prostate cancer receiving ADT at the MGH Cancer Center were surveyed for depression with the SCID for Axis I disorders for DSM-IV and the Beck Depression Inventory. Results: Major depressive disorder was prevalent in 12.8% of the men with prostate cancer receiving ADT, eight times the national rate of depression in men, 32 times the rate in men over 65 years old. Major depression was not associated with worsening disease, medical response to ADT, receiving chemotherapy, or the type of ADT. Past history of depression was associated with current depression in this population (p<0.000). No first onset cases of depression occurred on ADT in this sample. Conclusion: This data suggests a significant rate of major depression in men with prostate cancer receiving ADT and that men with past histories of depression may be at particular risk for recurrence of their depression while undergoing this treatment. Copyright © 2002 John Wiley & Sons, Ltd.