In recent years a novel family of interferon (IFN)-inducible nuclear proteins has been identified in both mouse and humans and implicated in the control of myeloid differentiation. Recent evidence suggests that this role may be mediated by an effect on cell cycle regulation through interaction with known transcriptional regulators. Our laboratory first identified a nuclear protein designated IFI 16, which is strongly inducible with IFN-alpha and -gamma in myeloid cells. IFI 16 shares homology with at least six IFN-inducible mouse genes, designated the Gene 200 cluster, and also has close similarity with the human myeloid cell nuclear differentiation antigen, whose expression has also been associated with later stages of normal myelopoiesis and some myeloid malignancies. The structural hallmark of each protein in this family of hemopoietic IFN-inducible nuclear proteins is a 200-amino acid motif (hence HIN-200), present singly or as a tandem repeat. The restricted expression of these proteins, their ability to bind to nucleic acid, and their expression in response to a variety of stimuli eliciting myeloid differentiation strongly suggest that they play a role in hemopoietic maturation.