AbstractThe effect of vitamin A deficiency on the carcinogenicity of betel quid was studied, using long‐term feeding of vitamin‐A‐deficient and‐sufficient diets with and without betel nut and calcium hydroxide in ACI rats. A high incidence of focal epithelial hyperplasia was observed in the upper digestive tract (tongue, buccal oral mucosa, esophagus, and forestomach) of rats in the group given the vitamin‐A‐deficient diet mixed with betel nut and calcium hydroxide. The vitamin‐A‐deficient group also showed a high incidence of squamous papilloma in the tongue, buccal mucosa, and forestomach. The incidence of hyperplastic lesions of the tongue and buccal oral mucosa was significantly higher in this group than in the group receiving the vitamin‐A‐sufficient diet with betel nut and calcium hydroxide. These results suggest that the vitamin‐A‐deficient condition enhanced the growth of epithelial hyperplasia that was due to the administration of the betel quid ingredients. However, vitamin A did not protect against the development of altered liver cell foci, which were frequently seen with a small number of hepatocellular neoplasms in all groups given the diets containing betel nut and calcium hydroxide (both vitamin‐A‐deficient and‐sufficient groups).