To evaluate possible involvement of a paracrine/autocrine inhibitory growth factor in myeloma cell growth, we studied the expression and actions of two forms of transforming growth factor beta (TGF-beta1 and TGF-beta2) on two closely related myeloma cell lines, OPM-1 and OPM-2. Earlier studies showed that both cell lines contain glucocorticoid receptors, but only OPM-2 cells are growth inhibited by dexamethasone (Dex). We found that OPM-2 growth was inhibited by TGF-beta, with TGF-beta1 exerting a greater effect than TGF-beta2, and Dex plus TGF-beta1 acting synergistically. In OPM-1 (Dex insensitive), TGF-beta mRNA was not expressed, whereas it was induced by Dex in OPM-2. It was also possible to block partially the growth inhibition of Dex in OPM-2 cells by the addition of anti-TGF-beta1 antibodies. These data suggest that the glucocorticoid effect(s) on myeloma cells may be mediated at least in part through modulation of internal and/or external levels of TGF-beta1.