Remission of precancerous lesions in the oral cavity of tobacco chewers and maintenance of the protective effect of beta-carotene or vitamin A. Participants in the intervention trials were fishermen (Kerala, India), who chewed tobacco-containing betel quids daily before and throughout the study period. Frequency of oral leukoplakia, micronuclei in oral mucosal cells, and alterations in nuclear textures were used as endpoints. Administration of vitamin A (60 mg/wk) for 6-mo resulted in complete remission of leukoplakias in 57% and a reduction of micronucleated cells in 96% of tobacco-chewers. beta-carotene (2.2 mmol/wk) induced remission of leukoplakia in 14.8% and reduction of micronucleated cells in 98%. Vitamin A completely suppressed and beta-carotene suppressed by 50% formation of new leukoplakia within the 6-mo trial period. After withdrawal of vitamin A or beta-carotene treatment, oral leukoplakias reappeared, frequency of micronuclei in oral mucosa increased, and nuclear textures reverted to those present before the administration of chemo-preventive agents. The protective effect of the original treatment could be maintained for at least 8 additional months by administration of lower doses of vitamin A or beta-carotene. 