In this study, we discussed the effects of treatment with recombinant adenovirus expressing p16 (AX-p16) on cell growth and cell death. Ax-p16 at 10 m.o.i. groups showed growth inhibition 3 days after gene transfection, but the cells regrew and did not undergo cell death. On the other hand, Ax-p16 at 300 m.o.i. groups showed complete cell growth inhibition leading to cell death which was apparent 7 days after p16 gene transfection. In the high m.o.i. Ax-mock groups, cell death was marked just after infection, but had diminished by 7 days after infection. Downregulation of pRB was detected only in Ax-p16 at 300 m.o.i. groups. These data suggest that a) high m.o.i. condition of Ax-p16 gives therapeutic benefits due to the combined effects of adenovirus and high expression of p16; and b) the cell killing mechanism of the p16 transgene is different from that of high m.o.i. adenoviral infection.