The modifying effects of nonylphenol and genistein on cancer induction were assessed in a multi-organ carcinogenesis model in male F344 rats initially treated with five different carcinogens. In experiment 1 rats received 250 or 25 ppm nonylphenol, or 250 or 25 ppm genistein in their diet for 28 weeks. The total incidences of adenomas and carcinomas in the lungs of animals treated with nonylphenol and genistein were significantly higher than in the control group. 5-Bromo-2'-deoxyuridine labeling indices, reflecting cell proliferation, were also significantly elevated in the lungs of rats given 250 and 25 ppm nonylphenol and 250 ppm genistein. In experiment 2, rats were treated with nonylphenol or genistein at concentrations of 250 ppm after DHPN initiation. In the lung, formation of 8-hydroxy-2'-deoxyguanosine, a marker of oxygen radical-mediated DNA damage, was significantly increased. These results indicate that nonylphenol and genistein have the potential to promote rat lung carcinogenesis, possibly via a mechanism involving stimulation of cell proliferation and DNA damage caused by oxygen radicals.