BACKGROUND: Depression has been shown to adversely affect the prognosis of patients with established coronary artery disease, but there is comparatively little evidence to document the role of depression in the initial development of coronary disease. METHODS AND RESULTS: Study participants were 409 men and 321 women who were residents of Glostrup, Denmark, born in 1914. Physical and psychological examinations in 1964 and 1974 established their baseline risk factor and disease status and their level of depressive symptomatology. Initial myocardial infarction (MI) was observed in 122 participants, and there were 290 deaths during follow-up, which ended in 1991. A 2-SD difference in depression score was associated with relative risks of 1.71 (P = .005) for MI and 1.59 (P < .001) for deaths from all causes. These findings were unchanged after we controlled for risk factors and signs of disease at baseline. There were no sex differences in effect sizes. CONCLUSIONS: High levels of depressive symptomatology are associated with increased risks of MI and mortality. The graded relationships between depression scores and risk, long-lasting nature of the effect, and stability of the depression measured across time suggest that this risk factor is best viewed as a continuous variable that represents a chronic psychological characteristic rather than a discrete and episodic psychiatric condition.