Large intestinal tumorigenesis was investigated in germ free (GF) mice following the administration of methylazoxymethanol (MAM) acetate, lard, and Lactobacillus arabinosus. Twelve weekly doses of 0.3 mg/10 g MAM acetate given to groups of male weanling, germfree ICR mice, fed either low-fat (LF) chow alone, or chow with added lard (HF). Additional groups of mice, on the low-fat diet, were monocontaminated with Lactobacillus arabinosus (GA) and they and their GF controls were given 12 weekly doses of 0.2 mg/10 g of MAM acetate. The HF and LF groups were sacrificed after 123 days, and the GA and GF groups after 214 days. Serial sections of the entire large intestine of the MAM acetate-treated mice revealed many more sessile polyps in the mice maintained on the high-fat diet. In the mice monocontaminated with Lactobacillus, numerous tumors were found, of which 25 percent were invasive. In addition, the polyps found in these animals were generally considerably larger than the polyps found in the GF mice. Atypia occurred in the large intestinal mucosa in all groups. Lard enhanced the large intestinal polypogenesis induced by MAM acetate in germfree mice. Gnotobiosis potentiated the formation of sessile polyps, and carcinogenesis.