Transforming growth factor beta (TGF beta) is an inhibitor of normal epithelial cell growth. To investigate the role of TGF beta in respiratory epithelial cell neoplasia, normal, preneoplastic, tumorigenic and tumor-derived rat tracheal epithelial (RTE) cells were plated in serum-free medium and grown in the presence of 0-300 pg TGF beta 1/ml. TGF beta 1 markedly inhibited the formation of colonies by primary RTE cells and some preneoplastic RTE cells. However, tumor-derived RTE cells were relatively resistant to TGF beta 1-induced growth inhibition. Resistance to TGF beta 1-induced growth inhibition, therefore, accompanies neoplastic progression of RTE cells.