We have identified a novel human gene (mig-6) that is rapidly induced upon mitogenic stimulation of quiescent fibroblasts. Serum induction is partially inhibited by protein synthesis inhibitors, indicating that mig-6 shares characteristics of both primary and secondary response genes. In contrast to most other mitogen-responsive genes, mig-6 mRNA expression is also regulated during normal cell cycle progression, showing a clear peak around mid-G1. Consistent with the regulation of mig-6 expression during the cell cycle, terminal differentiation of HL-60 cells to either granulocytic or macrophage-like cells also leads to clear changes in the levels of mig-6 mRNA. These observations suggest that the mig-6 gene represents a useful tool for the analysis of cell cycle progression and perhaps terminal differentiation. As a first step toward a functional characterization we show that the Mig-6 polypeptide is located in the cytoplasm.