We have previously shown that a fraction from a human placental extract, EAP, inhibited growth in soft agar of a human lung squamous adenocarcinoma cell line, A-2182, and of Ha-ras oncogene-transfected murine BALB/c 3T3 cells. We report here the activities of this extract on several cell lines which have different degrees of transformed phenotype. Human esophagus and colorectal cell lines were derived from tumors at different stages of neoplasic progression, and murine BALB/c 3T3 cells were transfected with various oncogenes. In all three models, growth of the most highly tumorigenic cells was inhibited by the presence of EAP in soft agar medium, while growth of non- and low tumorigenic counterparts was not affected or was stimulated by the placental extract. In addition, EAP did not significantly affect the doubling time of anchorage-dependent cell growth, suggesting that EAP specifically suppresses tumorigenic characteristics of cells such as their ability to grow in soft agar medium. These effects appear to be in contrast to those of transforming growth factor beta, which exerts its most profound effect on less tumorigenic cells.