This report presents the preliminary results of clinical studies designed to test Krumdieck's hypothesis that exposure to cigarette smoke results in folic acid deficiency affecting principally the bronchial epithelium through direct chemical inactivation, rendering it more susceptible to neoplastic transformation by the carcinogenic hydrocarbons of tobacco smoke. The background of the hypothesis is reviewed. Circulating vitamin levels of smokers with bronchial metaplasia were compared to those of nonsmokers and smokers without metaplasia. Significant differences found included lower levels of plasma and erythrocyte folate in smokers than in nonsmokers, and lower plasma folate levels in smokers with metaplasia than in smokers not having metaplasia. Similar but not statistically significant trends were noted for vitamin C, and no trends were seen in vitamins B12 and E, thiamine, riboflavin, pyridoxine, vitamin A, and carotene. This correlation of folate nutriture with a known premalignant condition suggests that the folate status of the bronchial mucosa may influence its susceptibility to neoplastic transformation.