Transforming growth factor-beta (TGF-beta) plays an important role in controlling proliferation or differentiation in almost all epithelial tissues. The pathophysiology of TGF-beta during carcinogenesis is now an important area of investigation, since it appears that as the process of carcinogenesis progresses, epithelial cells often become refractory to the growth-regulatory actions of TGF-beta. In this article we consider the possible cellular and molecular bases for this phenomenon, and then discuss some pharmacological approaches to enhancing the synthesis or activity of TGF-beta. These approaches may provide new modalities for prevention of carcinogenesis, if they can be applied during the early stages of the disease process, before cells become refractory. We give particular attention to tamoxifen and retinoic acid, since it has been shown that these agents, which are of known efficacy for prevention of cancer, can markedly enhance the secretion of specific isotypes of TGF-beta by several types of cells.