Intracardiac gene transfer and gene therapy have been investigated with different vector systems. Here we used adeno-associated virus (AAV) vectors to deliver either a reporter gene or a therapeutic gene into the heart of golden Syrian hamsters. The method of gene delivery was direct infusion of the AAV2 vectors into the coronary artery ex vivo in a heterotopically transplanted heart. When an AAV2 vector carrying the Lac-Z gene driven by CMV promoter was delivered into the heart of healthy hamsters, effective gene transfer was achieved in up to 90% of the cardiomyocytes. Lac-Z gene expression persisted for more than 1 year without immune rejection or promoter shutoff. Furthermore, when an AAV2 vector carrying human δ-sarcoglycan gene was similarly delivered into the heart of Bio14. 6 Syrian hamster, a congestive heart failure and limb girdle muscular dystrophy animal model, widespread therapeutic gene transfer was achieved in a majority of the cardiomyocytes. Efficient expression of the human δ-sarcoglycan gene in the dystrophic hamster hearts restored the entire sarcoglycan complex that was missing due to the primary deficiency of δ-sarcoglycan. Transgene expression persisted for 4 months (the duration of the study) without immune rejection or promoter shutoff. These results indicate that AAV is a promising vector system for cardiac gene therapy.