The antinuclear antibodies (ANA) test has been a cornerstone of the evaluation of connective tissue disease. The aim of this study was to investigate the diagnostic value of the ANA test in pleural or pericardial effusions of unknown causes. Over a 3-yr period, a total of 126 pleural fluid and 30 pericardial fluid samples were analysed. ANA tests were performed using a commercially available kit. The ANA kit used an indirect immunofluorescent antibody method with a human epithelial (HEP-2) cell line as substrate. Patients with high fluid ANA titre (>1:160) received a second aspiration 2 weeks after the initial aspiration if diagnosis was not confirmed. ANA results were positive in 39 pleural and 10 pericardial fluid samples. All but one of the effusions with positive ANA testing were exudative. Eleven pleural or pericardial effusions due to active systematic lupus erythematosus were identified and all had high ANA titres (1:160) with various staining patterns. Thirty-eight of 135 patients (26%) with effusions of nonlupus aetiologies had positive ANA testing in pleural or pericardial fluid. Thirteen of these 38 patients had high ANA titre, Malignant or paramalignant effusions constituted 11 of the 13 samples. In conclusion, although a negative antinuclear antibodies test makes a diagnosis of lupus serositis unlikely, high antinuclear antibodies titres in pleural or pericardial fluid are not diagnostic of lupus serositis when when as high as 1:5,120. An unexplained high antinuclear antibodies titre in pleural or pericardial effusion warrants search for malignancy.