The purpose of this study was to observe the effects of folate and vitamin B12 on bronchial squamous metaplasia with cellular atypia, known to be a precancerous change, in heavy smokers. Cases of squamous metaplasia were recognized on sputum cytologic study. The location of bronchial lesions was identified by bronchofiberoscopy in all cases. The grade of cellular atypia was evaluated on the basis of histologic specimens. Thirty-eight patients with squamous metaplasia, including 21 patients receiving folate and vitamin B12 and 17 patients without any medication, were investigated prospectively for 1 year. Consecutive bronchofiberoscopic examinations were performed in each patient in 3 to 4 months after the first examination in order to evaluate the lesions. Grades of cellular atypia were examined by histologic specimens using a scoring system from 0 to 3. There was no significant difference in mean scores at entry in the medication group (1.7) and control group (1.4). The medication group showed significant decrease in mean scores (0.4) while the control group had no change in mean scores (1.2) at termination. Plasma levels in the medication group were significantly increased at termination of the study while those of the control group showed a slight decrease. The results show that the cellular atypia squamous metaplasia in heavy smokers can be reduced by administration of folate and vitamin B12.