BACKGROUND AND OBJECTIVES: From the view point of the molecular aspects, the fate of long standing pressure and volume overloaded atrium in severe MR has not been evaluated. This study was performed to elucidate whether apoptosis of right atrial myocytes is related to atrial changes. SUBJECTS AND METHODS: The medical records of 16 patients (M: F=8: 8, mean age=52+/-12), with severe MR having undergone valve replacement surgery, were retrospectively reviewed. The subjects were divided into 2 groups according to the duration of their symptoms (group I, symptom duration less than 12 months, n=10 and group II, more than 12 months, n=6). Using the atrial myocardium specimens obtained during surgery, TUNEL assays and immunohistochemical staining were performed for the expressions of Fas, Bax and the Bcl family. RESULTS: Apoptotic indices of TUNEL assay were 31.1+/-12.6 and 4.9+/-4.3% in groups I and II, respectively (p<0.01). The Fas expressions were 42.1+/-14.4 and 27.8+/-10.5% in groups I and II, respectively (p<0.05), but in group I, with atrial fibrillation (AF), was 49.3+/-6.9%, which was higher than the 29.2+/-12.5% in group I without AF and group II (p<0.001). The Bax expression in group I patients with a left atrial size less than 4 cm was 19.2+/-10.7%, which was higher than the 7.2+/-6.2% in group I with a left atrial size more than 4 cm and group II (p<0.05). CONCLUSION: Programmed cell death of the atrial myocardium, in severe MR, might be an early molecular pathological change rather than the late sequelae. The causality between programmed cell death and electrical and structural changes of the atrium should be further investigated.