Changes in oxidative stress and apoptotic process were studied during the progression of a compensated hypertrophy to a decompensated heart failure in Guinea pigs. Banding of the ascending aorta resulted in heart hypertrophy. At 10 weeks, ventricle to body weight ratio and thickness of the interventricular septum as well as left ventricular wall were increased significantly. Although fractional shortening as well as ejection fraction were decreased, there were no signs of heart failure. Furthermore, there was no increase in wet to dry weight ratios for the lungs and the liver at this stage. However, at 20 weeks, heart failure was characterized by a significant depression in heart function as indicated by a decrease in the fractional shortening, ejection fraction and lesser increase in wall thickness from diastole to systole. Animals also showed clinical signs of heart failure and the wet to dry weight ratios of the lungs and liver were significantly higher. Cardiomyocyte oxidative stress was significantly higher in the 20 week aortic banded group. The ratio of Bax/Bcl-xl showed an increase at 10 weeks and there was further increase at 20 weeks. Mitochondrial membrane potential in the aortic banded animals was significantly decreased at 10 and 20 weeks. Cytochrome c levels were higher in the cytosol as compared to the mitochondria leading to a considerable increase in the expression of p17 subunit of caspase-3. At 20 weeks, both early and late stages of apoptosis were observed in isolated cardiomyocytes. It is suggested that an increase in oxidative stress initiates mitochondrial death pathway during the hypertrophic stage leading to apoptosis and heart failure at a later stage.