N-Acetylcysteine (NAC) is a soluble nucleophile that has been shown to have antimutagenic activity towards various genotoxic agents including 1,2-dimethylhydrazine (DMH). The present report extends such observations by showing the protective effect of NAC against the carcinogenic activity of DMH. This thiol-containing molecule reduced the incidence of rat intestinal tumors. Moreover, it significantly lowered the colic tumor yield as expressed by the number of tumors per rat bearing tumors. With regard to localisation of colic carcinomas, NAC induced a shift from distal to more proximal sites.