The action of high doses of cigarette smoke alone or combined with coal dust or acrolein was investigated in noninbred Sprague-Dawley rats. Inhalation occurred up to six sessions per day (Hamburg machine), the animals being subjected to a treatment with oxygen after each inhalation session to reduce the carbon monoxide level in the blood. The amount of tar found in the lungs depended on the number of inhalation sessions per day rather than on the total number of inhalations. Smoke inhalation caused emphysematous lesions, the extent of which depended on the total dose of smoke inhaled. No lung tumors were observed. Only a hyperplasia of the alveolar lining involving type II alveolar cells and, at a later stage, areas of metaplasia generally limited to the bronchial area were found. The association of coal dust with cigarette smoke did not alter the specific effects of smoke and resulted in effects peculiar to the action of dust: alveolitis of the macrophage type, fibrosis of the reticulin type, limited hyperplasia, and ciliated metaplasia. When smoke was combined with acrolein, the effects due to smoke were not appreciably altered.