OBJECTIVES: The economic burden of depression was estimated at approximately $44 billion in 1990. A subsequent study refined the estimation of the morbidity costs associated with depressive disorders and revised this figure to $53 billion. The objective of this study is to provide a 10-year update of the economic burden of depression using the same refined methodology. METHODS: Using a human capital approach we developed prevalence-based estimates of 3 major cost categories: 1) direct costs, 2) mortality costs arising from depression-related suicides, and (3) morbidity costs associated with workplace depression. Estimates were updated to reflect 2000 values, using the most current epidemiological data for prevalence rates and publicly available cost data by condition. RESULTS: We estimate that the total economic burden of depression in 2000 was $81.5 billion. Of this total, $26.1 billion - 32% - are direct medical costs, $5.4 billion - 7% - are mortality costs, and $49.9 billion - 61% - are morbidity costs. Work absenteeism resulted in $34.5 billion - 42% of total costs, while work cutback costs were $15.4 billion - 19% of total costs. CONCLUSIONS: The economic burden of depression was $81.5 billion in 2000. Morbidity generated the largest portion, 61%, of these costs. Future research investigations will incorporate additional costs associated with depressive disorders, including the excess costs of treating comorbid illnesses and the cost burden of depressed individuals' family members.