Interferon-regulatory factors (IRFs) are a related family of proteins originally identified by their ability to bind a DNA sequence found in the beta-interferon gene and many interferon-stimulated genes. Two well-studied members of this family, IRF-1 and IRF-2, have antagonistic roles in interferon-beta gene regulation: IRF-1 activates this gene, and IRF-2 represses the activation by IRF-1, IRF-1 and IRF-2 have more recently been linked to growth control by displaying tumor suppressor and oncogenic activities, respectively. A possible explanation for the oncogenic activity of IRF-2 is the discovery that IRF-2 can activate a histone gene that is functionally coupled to cell cycle progression. This first report of native IRF-2 playing the role of activator of a gene essential for growth may lead to the discovery of a more general involvement of interferon regulatory factors in mediating growth control.