Zinc has been shown to be required for the passage of cells through the mid-G1 phase of the cell cycle and for differentiation of myoblasts. However, it has been suggested that zinc has other roles during the cell cycle. The experiments reported here indicate that readily available zinc is not required for DNA synthesis per se but is needed for a process contemporaneous with the S phase and required for subsequent progress of the cells through G2 and mitosis. The G1 and S/G2 requirements for zinc showed virtually identical sensitivities to zinc deprivation. Each of the above requirements for zinc coincides with the induction of specific cyclin mRNAs, and the concentrations of these mRNAs have now been shown to decrease in the absence of adequate zinc. This is the first study to indicate a possible common factor underlying the requirement for available zinc during both cell replication and differentiation.