The expression level of the HMG2 gene during the cell cycle of rat fibroblast cell lines was analyzed. Northern analysis demonstrated that the level of HMG2 mRNA was markedly enhanced in the post-S phase and reached a maximum at G2 phase, suggesting that expression of the HMG2 gene is not coupled with DNA synthesis. Progression of the cell cycle of COS-1 cells was repressed during G1 to S phase by expression of the antisense RNA for HMG2, resulting in a decrease of cell growth. These results suggest that the fluctuation of the HMG2 message during the cell cycle is not a consequence of but a prerequisite for cell proliferation.