Background: Left ventricle burdened by longstanding volume-overloading undergoes various structural and functional alterations in the course of remodeling process. Accordingly, the expression of multiple classes of gene is likely to be altered. However, the profile of gene expression specifically in volume-overloaded left ventricle in human has not been explored. Methods and Results: Using a cDNA microarray, representing 4,600 cDNA clusters, we studied the pattern of gene expression in myocardium from 4 normal subjects and 5 patients with chronic regurgitant valvular heart disease whose end-diastolic left ventricular dimension measures more than 65 mm. We identified 60 differentially expressed genes in volume-overloaded myocardium that were functionally classifiable. Expression was altered in genes related to cell cycle/growth(11), signal transduction(6), transcription/translation(13), cell structure(10), metabolism(7), apoptosis(4), and other functions (9). Genes involved in cell cycle/growth(up-/down-regulation: 11/1), signal transduction(5/1) were mostly up-regulated in volume-overloaded myocardium. Distribution of expresssion was variable for genes involved in transciption/translation (up-/down-regulation: 6/7) and apoptosis (2/2). Of note, genes related to myocyte structure (troponin T3, myotubularin related protein, tropomyosin, etc) were down-regulated (up-/down-regulation: 0/10), as well as those for metabolism (2/5). The gene expression patterns of RT-PCR and immunohistochemistry from randomly selected genes showed similar pattern with those of cDNA microarray. Conclusions: Altered expression was identified in multiple genes involved in diverse functions in volume-overloaded human left ventricle. Genes related to cellular structure and metabolism were appeared to be down-regulated in dilated ventricle. These results might help elucidate cellular mechanism associated with remodeling process associated with chronic volume-overloading.