Background: Although right ventricular hypertrophy (RVH) is an adaptive process to stresses such as disturbances of outflow track obstruction, uncorrected, persistent RVH often results in failure of the right ventricle or even of the left ventricle. Recently, we reported that histone deacetylase (HDAC) inhibitors can effectively prevent or block left ventricular hypertrophy. The present study was aimed at extending our previous results with sodium valproate, an HDAC inhibitor, to RVH and to compare the effects of sodium valproate with those of captopril, an angiotensin-converting enzyme (ACE) inhibitor. Methods and Results: RVH was induced by pulmonary artery banding ( PAB) or by injection of monocrotaline in rats, and either sodium valproate or captopril was administered. Either PAB or monocrotaline injection caused a marked increase in the right ventricle after 2 weeks, which was documented by weighing the right ventricle, by evaluating echocardiograms or electrocardiograms, or by examining cardiac hypertrophy-associated gene expression. Sodium valproate significantly reduced RVH induced by either PAB or monocrotaline injection. Interestingly, however, captopril failed to do so. Conclusions: Sodium valproate (an HDAC inhibitor) but not captopril (an ACE inhibitor) was effective in blocking RVH induced by PAB or monocrotaline injection, which suggests that HDAC inhibitors may be a novel therapeutic for RVH.