Phosphoproteins were analyzed in human pre-erythrocyte leukemia cells transitting G_0 to S phase of the cell cycle. The protein of 110kDa of molecular weight was heavily phosphorylated in cells subjected to growth arrest at G_0 phase. An altered protein phosphorylation pattern was observed upon growth stimulation by refeeding serum to the cells. The newly phosphorylated proteins of 100 and 120kDa were detected during the transition period from G_0 to S phase entry. Upon the growth stimulation, the intracellular levels of Ca^(2+) and IP₃ second messenger molecules were suddenly elevated suggesting that signal cascades transmitted through the messenger molecules regulate the phosphorylation of specific proteins which are crucial for the maintenance of cell cycling.