Grapefruit, and isolated bioactive citrus compounds, are suggested to protect against some cancers. The ability of grapefruit pulp powder (irradiated or non-irradiated) and isolated compounds (apigenin, hesperidin, limonin, naringin, naringenin, nobiletin) to protect against colon cancer development were compared in Sprague Dawley rats. Rats were injected with saline or a colon carcinogen (azoxymethane, AOM, 15 mg/kg body weight, 2x, weeks 3 and 4) after starting the diets. All test diets, except hesperidin and nobiletin, reduced (P < 0.04) preneoplastic lesions (aberrant crypt foci, ACF) and increased (P < 0.05) apoptosis. Hesperidin, nobiletin and apigenin were the only diets that did not decrease (P < 0.04) proliferation of colonocytes. Untreated grapefruit pulp powder, limonin and naringenin prevented (P < 0.05) proliferative zone expansion in AOM-injected rats. The data indicate untreated grapefruit pulp powder, and certain isolated compounds, reduce ACF formation through changes in colonocyte proliferation and apoptosis. Because irradiated grapefruit pulp powder was not as effective as untreated grapefruit pulp powder in controlling proliferative zone expansion, it may not be as effective as untreated grapefruit pulp powder in colon cancer prevention.