Background Adenosine deaminase (ADA) and carcinoembryonic antigen (CEA) have been measured in pleural fluid to help distinguish malignant from benign effusions, especially in tuberculous pleurisy. We investigated ADA and CEA levels in patients with moderate to large pericardial effusions of different etiologies.Methods and Results We performed diagnostic and therapeutic pericardiostomy with drainage and biopsy. We measured ADA and CEA levels in the pericardial fluid in 26 patients with moderate to large pericardial effusion and 19 control patients. Patients were included in a prospective protocol from August 1991 to August 1993. Patients were grouped as follows: group 1, 9 patients with tuberculous pericarditis (TP) confirmed by bacteriologic culture or histology of pericardial biopsy; group 2, 5 patients with clinically strongly suspected TP; group 3, 12 patients with malignancy (8) and acute pericarditis (4); group 4, 19 control patients without pericardial disease. We treated patients with TP with isoniazid, rifampin, and either streptomycin or ethambutol for 12 months and pyrazinamide for 2 months. We observed for symptoms and signs of recurrent pericarditis or constrictive pericarditis on follow-up. In group 1 the ADA activity was significantly higher (101+-14 U/L) than that in group 3 (22+-5 U/L) or that in group 4 (17+-2 U/L) (P<.05). There was no significant difference between ADA activity in group 1 (101+-14 U/L) and that in group 2 (100+-26 U/L). With a cutoff value for ADA activity of 40 U/L, sensitivity was 93% and specificity 97% in the diagnosis of TP. In benign diseases, the CEA level was significantly lower (1.0+-0.3 ng/mL) than that in malignant diseases (135.1+-79.7 ng/mL) (P<.05). With a cutoff value for CEA level of 5 ng/mL, sensitivity was 75% and specificity 100% in the diagnosis of malignant pericarditis. Follow-up study (mean, 12.9, 19.8, and 11.8 months in groups 1, 2, and 3, respectively, showed no symptoms or signs of constrictive pericarditis, except for 1 patient.Conclusions Pericardial fluid ADA and CEA are useful for the differential diagnosis of pericardial effusion of various causes. They also have great value in early diagnosis of TP, particularly when the results of other clinical and laboratory tests are negative. (Circulation. 1994;89:2728-2735.)