Epidemiological and experimental evidence indicates a strong relationship between diet and cancer. The purpose of this study was to examine the potential of chlorophyllin (CHL), a food-grade derivative of the ubiquitous green plant pigment chlorophyll, to inhibit experimental carcinogenesis. We report that CHL is a potent, dose-responsive inhibitor of aflatoxin B1 DNA adduction and hepatocarcinogenesis in the rainbow trout model when fed with carcinogen. CHL neither promoted nor suppressed carcinogenesis with chronic postinitiation feeding. By molecular dosimetry analysis, reduced aflatoxin B1-DNA adduction accounted quantitatively for reduced tumor response up to 2000 ppm dietary CHL, but an additional protective mechanism was operative at 4000 ppm CHL. The finding of potent inhibition (up to 77%) at CHL levels well within the chlorophyll content of some green leafy vegetables may have important implications in intervention and dietary management of human cancer risks.