Background: The aim of this study was to establish the diagnostic accuracy of neutrophil markers (elastase, lysozyme, myeloperoxidase) found in pleural fluid in differentiating between infectious and non-infectious pleural effusions (PE). Methods: We studied 184 patients over 18 years of age with PE, classified as either infectious (34 complicated parapneumonic, 32 non-complicated parapneumonic, 45 tuberculous) or non-infectious (31 neoplasms and 42 undiagnosed exudates). Polymorphonuclear elastase (PMN-E) was determined using an immunoactivation method and lysozyme using a turbidimetric method. Myeloperoxidase (MPO) was measured by double antibody competitive radioimmunoassay. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy. Results: Pleural fluid MPO was the biochemical marker that best differentiated between infectious and non-infectious PE. The ROC area under the curve (AUC) for myeloperoxidase was 0.86. MPO values over 550 &mgr;g/l diagnosed infectious PE with a specificity of 90.4% and a sensitivity of 77.4%. After excluding purulent parapneumonic PE, the sensitivity of a pleural MPO value >/=550 &mgr;g/l was 72.6%. Conclusions: Pleural fluid MPO was the marker that best differentiated between infectious and non-infectious PE.