We showed previously that vitamin A deficiency per se causes emphysema. Benzo(a)pyrene, a constituent in cigarette smoke, induces vitamin A depletion when administered to rats; therefore, we tested the hypothesis that cigarette smoke induces vitamin A depletion, which is associated with the development of emphysema. Male weanling rats were fed a purified AIN-93G diet and divided into two groups. The experimental group was exposed to cigarette smoke from 20 nonfiltered commercial cigarettes/d for 5 d/wk, whereas the control group was exposed to air. After 6 wk, tissues were collected for histological and biochemical analyses. Retinol levels were measured in serum, lung and liver. The trachea, lung and liver were examined for histological changes. Vitamin A levels decreased significantly in serum, lung and liver of smoke-treated rats. Histological examination revealed the presence of interstitial pneumonitis along with severe emphysema. There was a significant inverse relationship between vitamin A concentration in the lung and the severity of emphysema (r = -0.69 and P < 0.03). Detachment or hyperplasia (and metaplasia) of the tracheal epithelium and liver vacuole formation also were evident in the smoke-treated rats. The results of this research indicate that exposure to cigarette smoke induces vitamin A depletion in rats, which is associated with the development of emphysema.