Transforming Growth Factor beta is a potent autocrine inhibitor of the growth of untransformed keratinocytes. We found each of eight human squamous carcinoma cell lines to be refractory to the anti-proliferative action of Transforming Growth Factor beta. Although each of these carcinoma cell lines expressed the 53-65 kDa (type I) and the 280-300 (type III) Transforming Growth Factor beta-receptor proteins, the 73-85 kDa (type II) species was detectable in only one of these cell lines. Furthermore, although Transforming Growth Factor beta-sensitive non-neoplastic mouse keratinocytes expressed type II binding proteins, human keratinocytes did not. Our findings suggest that resistance to the growth-inhibitory actions of Transforming Growth Factor beta is a common feature of human squamous carcinoma cell lines but does not correlate with the expression of cell-surface receptors for this growth factor.