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The first step in the evaluation of patients with pleural effusion is to determine whether the effusion is a transudate or an exudate. An exudative effusion is diagnosed if the patient meets Light’s criteria. The serum to pleural fluid protein or albumin gradients may help better categorize the occasional transudate misidentified as an exudate by these criteria. If the patient has a transudative effusion, therapy should be directed toward the underlying heart failure or cirrhosis. If the patient has an exudative effusion, attempts should be made to define the etiology. Pneumonia, cancer, tuberculosis, and pulmonary embolism account for most exudative effusions. Many pleural fluid tests are useful in the differential diagnosis of exudative effusions. Other tests helpful for diagnosis include helical computed tomography and thoracoscopy. (Am Fam Physician 2006;73:1211–20. Copyright © 2006 American Academy of Family …