The effect of transforming growth factor β 1 (TGF-β1) on levels of hepatocyte growth factor/scatter factor (HGF/SF) gene transcripts was investigated in the human lung embryonic fibroblast cell line, MRC-5. TGF-β1 markedly reduced the expression of the 6.0-kb and 3.0-kb HGF/SF mRNA, which encode full-length HGF/SF, but it had little effect on the expression of the alternatively spliced 1.5-kb mRNA, which encodes NK2, a competitive HGF/SF antagonist. Using actinomycin D to block RNA synthesis, it was observed that TGF-β1 had little effect on the stability of the 1.5-kb NK2 mRNA but increased the rate of degradation of the 6.0- and 3.0-kb HGF/SF mRNA transcripts by a mechanism that was dependent on new protein synthesis. TGF-β1 minimally increased rather than reduced HGF/SF promoter activity in cells transiently transfected with chloramphenicol acetyltransferase (CAT) reporter genes driven by HGF/SF gene 5′-flanking sequences. In MRC-5 cells, TGF-β1 modulates HGF/SF gene transcripts at the posttranscriptional level in order to favour expression of the 1.5-kb mRNA that encodes the truncated protein NK2.