The bacillary population described in tuberculous pleuritis is small, and its most likely pathogenetic mechanism is essentially immunologic. This explains why, until now, the diagnostic identification of tuberculous pleuritis (TP) has been based on the presence of granulomas in pleural biopsy. Correcting this diagnostic deficiency through other parameters related to the specific pathogenetic mechanism has been widely studied. The determination of the levels of adenosine deaminase (ADA) in pleural fluid offers high performance in its discriminating capacity to identify TP (sensitivity 87 to 100%, specificity 81 to 97%). Adenosine deaminase expresses the sum of two isoenzymes (ADA1 and ADA2). ADA1 is ubiquitous in all cells, including lymphocytes and monocytes, whereas ADA2 is found only in monocytes. Analysis and determination of these isoenzymes have shown that ADA in TP increases particularly at the expense of ADA2 and that the ADA1 /ADAp activity ratio improves performance in terms of sensitivity, specificity, and efficacy (100%, 92 to 97%, and 98%, respectively) in correcting all false-negative and false-positive results except 1 to 9% of nonlymphoproliferative malignancies. Only the high performance of ADA in the identification of TP allows it to be assumed that pleural biopsy can be obviated, especially in patients aged less than 35 years of age or having a lymphocyte-to-neutrophil proportion of more than 0.75 in regions of high prevalence. Quick determination and low cost justify its routine use in exudates. The ADA1 /ADAp activity ratio improves performance even more and could be used in cases with uncertain diagnoses or in regions with low prevalence of tuberculosis.