Adenoviruses are promising vectors for gene therapy. The production of adenoviral vectors (AdV), however, is limited by the cell density effect, namely when cell infection is performed at above 10(6) cells/ml, a drop in cell-specific adenovirus productivity occurs. Our results also show that the coxsackie adenovirus receptor (CAR) plays an important role in AdV production. CAR expression of infected cells varied with culture time and the cell-specific AdV productivity dropped rapidly along with decreased CAR expression. Furthermore, CAR expression of cells was maintained at a high level by replacing the medium or supplementing it with trichostatin A, which could improve the cell-specific productivity. Thus, a higher CAR expression level at infection time could improve cell-specific AdV productivity at high cell densities.