Major depression is associated with adverse outcomes in patients who have coronary heart disease. How best to identify depression in busy cardiology practices is unknown. We compared the test characteristics of 4 depression screening instruments with an interview diagnosis of depression (Diagnostic Interview Schedule) in 1,024 outpatients who had coronary heart disease. Screening instruments were the 10-item Center for Epidemiologic Studies Depression Scale-10, the Patient Health Questionnaire-9, the Patient Health Questionnaire-2, and a simple 2-item instrument that asks (1) "During the past month, have you often been bothered by feeling down, depressed, or hopeless?" and (2) "During the past month, have you often been bothered by little interest or pleasure in doing things?" Of the 1,024 participants, 224 (22%) had major depression based on the Diagnostic Interview Schedule. Areas under the receiver-operating characteristic curves were similar for all instruments (range 0.84 to 0.87). In conclusion, a positive response to 1 of the 2 items was 90% sensitive and 69% specific for depression, with a negative likelihood ratio of 0.14. Thus, negative responses to the 2 items effectively ruled out depression. A score > or =10 on the Patient Health Questionnaire-9 was 54% sensitive and 90% specific, with a positive likelihood ratio of 5.4. Thus, a cutpoint > or =10 was virtually diagnostic for depression.