We aimed to investigate whether pleural fluid concentrations of biomarkers for bacterial infection, namely triggering receptor expressed on myeloid cells (sTREM-1), procalcitonin (PCT), lipopolysaccharide-binding protein (LBP) and C-reactive protein (CRP), might identify infectious effusions and discriminate between complicated (CPPEs) and uncomplicated parapneumonic effusions (UPPEs). Stored pleural fluid samples from 308 patients with different causes of pleural effusion were used to measure the four biomarkers. Receiver-operating characteristic analysis determined the accuracy of the new tests. Median pleural fluid levels of CRP, sTREM-1 and LBP were significantly higher in CPPE compared with those in other aetiologies. The area under the curve for distinguishing infectious (parapneumonics and tuberculosis) from noninfectious effusions was 0.87 for CRP, 0.86 for sTREM-1, 0.57 for PCT and 0.87 for LBP. Regarding the discrimination of nonpurulent CPPE versus UPPE, a multivariate analysis found that pleural fluid glucose < or =60 mg x dL(-1), LBP > or =17 microg x mL(-1) and CRP > or =80 mg x L(-1) were the best parameters. Individually, none of the new biomarkers achieved better performance characteristics than pH, glucose or lactate dehydrogenase in labelling CPPE. In conclusion, elevated pleural fluid levels of CRP, sTREM and LBP identify patients with infectious effusions, particularly those with CPPE. PCT has no value for the differential diagnosis of pleural effusions.