The interferon (IFN)-induced enzyme 2′,5′-oligoadeny late (2-5A) synthetase has been implicated in the development of antiviral activity in human and animal cells. However, its role in IFN-mediated growth inhibition remains unclear. To elucidate the function of 2-5A synthetase, we have stably introduced a human 2-5A synthetase cDNA into a human glioblastoma cell line (T98G). Constitutive expression of the cDNA in these cells is associated with increased levels of resistance to infection by encephalomyocarditis virus. One transfected subclone, which expresses elevated levels of 2-5A synthetase enzyme activity, also shows a reduced rate of cellular proliferation.