A large dietary supplement (1%) of vitamin C was given to male Syrian hamsters exposed to cigarette smoke and receiving 12 weekly subcutaneous injections of diethylnitrosamine (DEN) to determine whether or not high doses of vitamin C can prevent the development of tumors by DEN in the respiratory tract. Treatment with DEN developed various types of tumors in the respiratory tract of hamsters and cigarette smoke exposure potentiated the tumor development in the nasal cavity, larynx and trachea. In comparison with the smoke-exposed hamsters treated with DEN, the vitamin C-supplemented hamsters showed significantly lower incidence of nasal cavity tumors and exhibited significantly earlier appearance of tracheal tumors. In addition, the laryngeal tumors also tended to develop earlier in the vitamin C-supplemented hamsters. The results indicate that high doses of vitamin C may inhibit tumor induction by DEN and exposure to cigarette smoke in the nasal cavity, but the development of laryngeal and tracheal tumors appeared to be accelerated by vitamin C supplement.