AbstractMale Fischer 344 rats were fed a 20% or a 5% corn oil diet and were injected subcutaneously with dimethylhydrazine (DMH) weekly for 16 weeks. In addition, an approximately equal number of animals challenged with DMH were fed daily, until the end of the study, 2×1010Lactobacillus casei subsp. rhamnosus strain GG starting three weeks before DMH administration or after the ninth weekly injection. The feeding of the Lactobacillus GG before and during carcinogen treatment resulted in a significant decrease in the incidence of colon tumors and the number of small intestinal and colon tumors per tumor‐bearing animal for rats fed a 20% corn oil diet. This decrease in tumor incidence or number of tumors was not seen when animals were fed the Lactobacillus after the ninth week of carcinogen treatment. Animals fed a 5% corn oil diet had a lower tumor incidence and number of tumors resulting from the decrease in dietary fat; in addition the feeding of Lactobacillus GG before the carcinogen challenge resulted in a lower incidence of colon tumors. These studies show that a specific strain of L. casei subsp. rhamnosus designated GG can interfere with the initiation or early promotional stages of DMH‐induced intestinal tumorigenesis, and this effect is most pronounced for animals fed a high‐fat diet.