To investigate the clinical significance of carbohydrate antigen 125 (CA125), an antigen related to ovarian cancer, in patients with pericardial effusion, we examined the relationship between serum levels of CA125 and the presence or severity of pericardial effusion. Fifty-seven patients (25 with heart failure, 22 with pericardial metastasis, 4 with hypothyroidism, 4 with renal failure, and 2 with other diseases) in whom pericardial effusion was confirmed by echocardiography or autopsy, were used as subjects. Thirty-seven of these patients (65%) tested positive for CA125 in the serum. Of these, no significant differences in serum levels of CA125 were found between patients with benign and those with malignant underlying diseases or between those with, or without, pericarditis. However, CA125 values were higher in the patients with larger pericardial effusions and the serum level decreased when the pericardial effusion reduced. In some cases, the serum level normalized before the effusion resolved. Pericardial drainage was performed on 6 patients with cardiac tamponade. Four of these 6 patients had high serum CA125 levels and recurrent pericardial effusion. The other 2 patients had normal serum CA125 levels and no recurrence of effusion. An immunohistological study showed that a positive stain of pericardial tissues reacting to CA125 antibodies correlated to higher serum and pericardial fluid levels of CA125 than the levels of groups staining negative to the antibody. These results suggest that CA125 can be useful in assessing the status and clinical course of this disease.