Carbohydrate antigen 125 (CA 125), known as a tumor marker for ovarian cancer, has been reported to increase and relate to severity in heart failure patients with systolic dysfunction. Hypertrophic cardiomyopathy (HCM) has a wide clinical spectrum that often includes heart failure symptoms. The aim of this study was to evaluate the role of CA 125 in HCM patients, its relation to severity of symptoms, and degree of diastolic dysfunction. CA 125 blood levels were determined in 32 HCM patients (21 male; age 51.3 +/- 18.4 years) and in 30 healthy volunteers (19 male; age 49.6 +/- 16.1 years). Echocardiographic examinations were performed in all patients. The results were grouped according to clinical status (New York Heart Association class) of the patients. The mean serum level of CA 125 was 14.6 +/- 23.8 U/ml in the study group and 7.6 +/- 4.8U/ml in the control group. There was no significant difference between the groups (P = 0.12). CA 125 levels increased as the New York Heart Association functional class increased (class I/II: 6.2 +/- 2.4U/ml; class III: 30.6 +/- 36.4U/ml; P < 0.001). The mean CA 125 level in functional class III patients (30.6 +/- 36.4U/ml) was significantly higher than that of the control group (7.6 +/- 4.8U/ml) (P < 0.001) and the functional class I/II group (6.2 +/- 2.4U/ml) (P < 0.001). There was a significant difference over all three diastolic dysfunction groups with respect to CA 125 levels (4.9 +/- 1.3U/ml in impaired relaxation group, 11.8 +/- 6.9 U/ml in pseudonormal group, and 52.6 +/- 45.6U/ml in restrictive filling group; P < 0.0001). Serum CA 125 is related to the clinical severity of HCM. Whether CA 125 has a specific biological role in HCM requires further investigation.