Tumor necrosis factor (TNF) induces the synthesis of two proteins of Mr 42 and 36 kDa in human fibroblasts and SK-MEL-109 melanoma cells. To identify these proteins, a lambda gt10 cDNA library was prepared from the mRNA of TNF-treated SK-MEL-109 cells. By screening this library, we found a cDNA that preferentially hybridized to TNF-induced RNA. Hybrid-selected mRNA was translated into a protein of 42 kDa; cDNA sequence analysis followed by a comparison with other known protein sequences identified this protein with plasminogen activator inhibitor, type-2 (PAI-2). After removal of TNF, PAI-2 mRNA turned over rapidly, with an apparent half-life of approximately 2.5 h. Addition of dexamethasone increased the turnover of this mRNA, suggesting that the level of PAI-2 mRNA could be regulated post-transcriptionally by glucocorticoids. PAI-2 was not secreted, but accumulated in fibroblasts continuously treated with TNF.