Congestive heart failure is the most common cause of death in young adults with thalassaemia major. In the present study we compared atrial natriuretic peptide levels (ANP) in 30 asymptomatic patients with thalassaemia major (aged 16.6 +/- 6.4 years), normal left ventricular diastolic cavity dimension and systolic function, with 30 aged and sex matched normal control subjects. ANP levels were significantly higher in patients with thalassaemia major compared to controls (93.9 +/- 26.3 pg.ml-1 vs 51.8 +/- 26.5 pg.ml-1; P < 0.001). Plasmatic renin activity, aldosterone, urinary sodium and catecholamine levels at basal conditions did not differ significantly in these two groups (ns). Blood volume stimulation (blood transfusion) in thalassaemic patients was followed by an increase of mean ANP values (93.9 +/- 26.3 to 109.1 +/- 40.5 pg.ml-1; P < 0.03). ANP basal levels above two standard deviations of the mean values obtained in normal control subjects were considered as abnormal and found to be in close correlation with the presence of diastolic dysfunction of the left ventricle identified by Doppler echocardiography. The method has a 57% sensitivity and a 91% specificity for revealing pre-clinical cardiac involvement (P < 0.02). Although a longer observation period is necessary in order to define the clinical and prognostic significance of these data, our results show that an increase in ANP basal values is present in asymptomatic patients with thalassaemia major. This suggests initial myocardial involvement, while ANP response to volume overload is maintained.