Effects of phenyl N-tert-butyl nitrone (PBN), a spin-trapping agent, on the development of frank cancers were examined in male Wistar rats fed with a choline-deficient, l-amino acid-defined (CDAA) diet for 70 weeks. PBN (0.065% in the drinking water) reduced incidences, multiplicities and possibly sizes of both hepatocellular adenomas and carcinomas when administered for all 70 weeks or only for the first 26 weeks, and those of carcinomas but not adenomas, when administered only for the last 44 weeks. These results indicate that PBN can prevent the development of frank HCCs in the CDAA diet model. The anti-carcinogenic effect of PBN may be ascribed to the prevention of both the development of HCAs and their malignant conversion to HCCs. If such findings can be generalized, PBN may be able to serve as a good tool to investigate molecular mechanisms underlying carcinogenic processes.