The aim of this study was to determine whether pleural fluid C-reactive protein (CRP) is useful in distinguishing complicated parapneumonic pleural effusion (CPPE) and empyema from uncomplicated parapneumonic pleural effusions (UPPE). A total of 69 consecutive patients with parapneumonic effusions were enrolled in the study: 29 with UPPE, 29 with CPPE, and 11 with empyema. Concentrations of standard biochemical parameters together with CRP in the pleural fluid were measured using an immunoturbidimetric assay. Pleural CRP was significantly higher in CPPE (11.6 mg/dl) and in empyema (12.2 mg/dl) than in UPPE (3.9 mg/dl). A cutoff value of 8.7 mg/dl for pleural CRP in the diagnosis of CPPE and empyema resulted in a sensitivity, specificity, and area under the receiver-operating characteristic curve (AUC) of 0.80, 0.97 and 0.94, respectively. Traditional lactic dehydrogenase (LDH) > or = 1000 U/L and glucose < or = 60 mg/dl can differentiate CPPE and empyema from UPPE, with the sensitivity, specificity, and AUC achieving 0.75/0.60.1.00/1.00,0.95/0.22, respectively. However, for the detection of CPPE and empyema, the combination of pleural fluid CRP > or = 8.7 mg/dl and LDH > or = 1000 U/L was valuable in achieving a sensitivity, specificity, and AUC of 0.97/1,00/0.95. This study suggests that measurement of pleural CRP can be useful in the workup of patients with a parapneumonic effusion in order to differentiate CPPE from UPPE.