METHODS Tygerberg Hospital, an academic teaching hospital, Republic of South Africa. OBJECTIVE To identify the adenosine deaminase (ADA) isoenzymes as a diagnostic tool for tuberculosis in pleural effusions with increased ADA activity. METHODS Patients (n = 157) with exudative effusions and ADA activities >20 U/l, due to causes which satisfied predetermined diagnostic criteria, participated in the study. They consisted of 87 tuberculous effusions, 27 infective effusions (12 empyematous and 15 non-empyematous), 37 malignant effusions and six other exudative effusions (systemic lupus erythematosus, pancreatitis and lung embolus). In each case the ADA isoenzymes in the pleural fluid were identified using polyacrylamide gel electrophoresis. In addition, microbiology and cytology (including differential cell counts) were also carried out. RESULTS Although ADA1c and ADA2 were the predominant isoenzymes observed in tuberculous effusions, while ADA1c and ADA1m were predominant in infective non-empyematous effusions, no additional diagnostic value was obtained. In the case of neoplastic effusions and other exudates, determination of ADA isoenzyme patterns also did not assist in diagnosing these conditions. CONCLUSIONS Determination of patterns of ADA isoenzymes does not enhance the overall diagnostic value of ADA activity in pleural effusions.