AbstractTransforming growth factor-beta (TGF-β) is produced by a number of tumor cell types including human malignant mesothelioma (MM), but its role as a direct or indirect factor in tumorigenesis is incompletely understood. We have investigated the expression of TGF-βisoforms by human and murine MM cells and have analysed the effects of inducible antisense RNA-mediated inhibition of TGF-βexpression on murine MM in vitro and in vivo. The results showed that (a) TGF-βand -β2 were produced by both human and mouse MM cells, (b) antisense RNA against either TGF-β1 or -β2 cross-inhibited both TGF-β1 andβ2 expression, (c) inhibition of TGF-βexpression reduced the anchorage-independent growth of MM cellsin vitroand the tumorigenicity of MM cellsin vivo, and (d) inhibition of TGF-βexpression led to increased T lymphocyte infiltration into tumors. The data suggest that TGF-βhas multiple tumor-enhancing effects in MM.