The diagnostic criteria for depression were developed on the basis of clinical experience rather than empirical study. Although they have been available and widely used for many years, few studies have examined the psychometric properties of the DSM criteria for major depression. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we examined whether criteria such as insomnia, fatigue, and impaired concentration that are also diagnostic criteria for other disorders are less specific than the other DSM-IV depression symptom criteria. We also conducted a regression analysis to determine whether all criteria are independently associated with the diagnosis of major depressive disorder. A total of 1538 psychiatric outpatients were administered a semistructured diagnostic interview. We inquired about all of the symptoms of depression for all patients. All of the DSM-IV symptom criteria for major depressive disorder were significantly associated with the diagnosis. Contrary to our prediction, symptoms such as insomnia, fatigue, and impaired concentration, which are also criteria of other disorders, generally performed as well as the criteria that are unique to depression such as suicidality, worthlessness, and guilt. The results of the regression analysis, which controlled for symptom covariation, indicated that five symptoms (increased weight, decreased weight, psychomotor retardation, indecisiveness, and suicidal thoughts) were not independently associated with the diagnosis of depression. The implications of these results for revising the diagnostic criteria for major depression are discussed.