Detailed comparative studies were conducted on the progressive increase in stainable iron deposition in normal, preneoplastic, and neoplastic tissues of rats fed diets containing 8-hydroxyquinoline (HQ), with or without further supplements of iron as ferrous gluconate (FG). As previously reported, HQ induced hepatic iron deposition and this was enhanced by FG at all time points. However, even very minimal liver lesions induced by the hepatocarcinogens diethylnitrosamine or N-2-fluorenylacetamide, barely recognizable by standard hematoxylin and eosin staining techniques, stood out clearly because they did not accumulate stainable iron like the adjoining hepatocytes. Hepatic hyperplastic and neoplastic lesions of increasing severity seen during continuing carcinogen treatment characteristically did not exhibit siderosis. Thus iron stains in the livers of rats fed HQ and FG permit the sensitive and reliable detection of early hyperplastic or neoplastic lesions. Rats ingesting HQ in addition to the carcinogens had a lower incidence of hepatic malignancy.