TTK is a novel protein kinase detectable in all proliferating human cells and tissues. Expression of the TTK gene is markedly reduced or absent in resting cells and in tissues with a low proliferative index. In view of the apparent association between TTK gene expression and cell proliferation, we examined the regulation of this protein kinase during transit of the cell cycle. We found very low levels of TTK mRNA and protein in starved cells. When cells are induced to enter the cell cycle, levels of TTK mRNA, protein and kinase activity increase at the G1/S phase of the cell cycle and peak in G2/M. TTK mRNA levels, as well as kinase activity, drop sharply in early G1, whereas protein levels are largely maintained. TTK may play a role in cell cycle control.