BACKGROUND Tuberculosis kills five lakh patients every year in India, commonest being pulmonary tuberculosis and is often associated with effusion. Delay in diagnosis and treatment results in poor prognosis. Several studies have suggested the role of adenosine deaminase (ADA) in the diagnosis of tuberculous pleural effusions, but false-positive results from lymphocytic effusions have also been reported. The purpose of this study is to find out the role of ADA levels in differentiation of tuberculous and non-tuberculous exudative pleural effusions of different etiologies. METHODS Ninety-six lymphocytic pleural fluid samples were consecutively selected and divided into two groups: tuberculous (n = 56) and non-tuberculous (n = 40), depending upon the etiology [Malignancy (n = 16), Infectious diseases (n = 18), Pulmonary embolism (n = 1), Collagen vascular diseases (n = 3) and Sarcoidosis (n = 2)]. ADA was estimated in pleural fluid in all the cases. RESULTS In all 56 samples, ADA level of tuberculous group was above diagnostic cut-off (40 U/L), while only one sample was above cut-off in non-tuberculous group (2.5%). The negative predictive value of ADA for the diagnosis of non-tuberculous etiology was 97.5% (39 of 40) lymphocytic pleural effusion patients. CONCLUSIONS In this study, ADA levels in nontuberculous exudative pleural effusions rarely exceeded the cut-off; set for tuberculous disease. The pleural fluid ADA levels were significantly higher in tuberculous exudative pleural effusions when compared with non-tuberculous exudative pleural effusions. BACKGROUND Adenosine deaminase; Tuberculous effusion; Pleural fluid; Exudative pleural effusions.