Specific stages of the prereplicative G1 phase of the cell cycle in nonneoplastic cells requires extracellular Ca2+ for successful transition. These are the G0-G1 and the G1-S transitions. A variety of agents are able to replace Ca2+ and to at least partially stimulate cells to replicate their chromosomes. One of these agonist, inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4], has been demonstrated by us to also stimulate the activity of a phosphoprotein phosphatase. The addition of a purified preparation of the protein phosphatase to Ca2+-deprived G1-S-blocked T51B rat liver cells stimulates a rapidly responding fraction of cells to enter their S phase, and this effect is blocked by protein phosphatase inhibitors heparin and inhibitor 2. © 1990.