Interferons (IFNs) are a family of multifunctional cytokines thatactivate transcription of subsets of genes. The gene products inducedby IFNs are responsible for IFN antiviral, antiproliferative, andimmunomodulatory properties. To obtain a more comprehensive list and abetter understanding of the genes regulated by IFNs, we compiled datafrom many experiments, using two different microarray formats. Thecombined data sets identified >300 IFN-stimulated genes (ISGs). Toprovide new insight into IFN-induced cellular phenotypes, we assignedthese ISGs to functional categories. The data are accessible on the World Wide Web at http://www.lerner.ccf.org/labs/williams, including functional categories and individual genes listed in asearchable database. The entries are linked to GenBank and Unigenesequence information and other resources. The goal is to eventuallycompile a comprehensive list of all ISGs. Recognition of the functionsof the ISGs and their specific roles in the biological effects of IFNsis leading to a greater appreciation of the many facets of theseintriguing and essential cytokines. This review focuses on thefunctions of the ISGs identified by analyzing the microarray data andfocuses particularly on new insights into the protein kinaseRNA-regulated (PRKR) protein, which have been made possible with theavailability of PRKR-null mice.