OBJECTIVE We aimed to investigate adenosine deaminase (ADA) activity and the activities of its ADA1 and ADA2 isoenzymes in pleural effusions and also sera with different aetiological origins. METHODS The pleural effusions of 87 patients were examined. The patients were separated into four groups: transudates, parapneumonic, malignant, and tuberculous effusions. The cases were also designated as tuberculous or non-tuberculous group. Adenosine deaminase activity was determined by the colorimetric method described by Giusti and Galanti. RESULTS The intermean differences were statistically significant for total ADA, ADA1 and ADA2, except for pleural fluid ADA1 in the malignant group when compared to the tuberculous effusion group. The intermean differences between the tuberculous and non-tuberculous group were statistically significant for all three parameters except for pleural fluid and serum ADA1 activity. The sensitivities of total ADA, ADA1 and ADA2 activities for tuberculosis were 91, 57 and 93%, respectively; their specificities 89, 88 and 92%, respectively; their positive predictive values 82, 70 and 86%; and their diagnostic accuracies 89, 76 and 92%, respectively, in pleural fluid. CONCLUSIONS Determination of ADA and its isoenzymes can help to differentiate the causes of pleural effusion. Increased ADA2 activity is a striking marker of tuberculous effusions. In contrast, increased ADA1 activity was significantly elevated in parapneumonic effusions.