Cells prepare for S phase during the G₁ phase of the cell cycle. Cell biological methods have provided knowledge of cycle kinetics and of substages of G₁ that are determined by extracellular signals. Through the use of biochemical and molecular biological techniques to study effects of growth factors, oncogenes, and inhibitors, intracellular events during G₁ that lead to DNA synthesis are rapidly being discovered. Many cells in vivo are in a quiescent state (G₀), with unduplicated DNA. Cells can be activated to reenter the cycle during G₁. Similarly, cells in culture can be shifted between G₀ and G₁. These switches in and out of G₁ are the main determinants of post-embryonic cell proliferation rate and are defectively controlled in cancer cells.