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Depressed mood syndromes may limit the ability of patients with sexually transmitted diseases (STDs) to process risk reduction messages and change behavior. We undertook screening for depression in an urban STD clinic.To define the prevalence of depressed mood among STD patients in Baltimore, Maryland.A convenience sample of 125 patients presenting to an STD clinic completed the 30-item General Health Questionnaire (GHQ). Endorsement of ≥ 6 depressive symptom items on the GHQ was considered probable depression.Of 125 patients screened, 39.2% had GHQ scores above the threshold. Women were more likely to have probable depression than men (51.9% versus 31.9%, P = 0.023). There was no association of substance use and depressed mood, nor of a diagnosed STD and depressed mood.Depressive symptom rates are extremely high among STD patients, which may compromise the success of risk reduction counseling.