Loss of sensitivity to growth inhibitory polypeptides is likely to be one of the events that participates in the formation of some tumors and might be caused by inactivation or loss of the genetic elements that transduce these extracellular signals. The isolation of such a gene was achieved by randomly inactivating genes by an anti-sense complementary DNA expression library followed by direct selection for growth in the presence of an inhibitory polypeptide. Thus, a gene whose inactivation conveyed growth resistance to interferon-gamma (IFN-gamma) was isolated. Sequence analysis showed complete identity with human thioredoxin, a dithiol reducing agent, implicated here in the IFN-gamma-mediated growth arrest of HeLa cells.