Natural killer (NK) cells play a central role in immune surveillance against tumors and viral infections. NK activity is depressed in patients who have a wide range of carcinomas, including carcinomas of the lung. Peripheral blood NK activity was measured in 22 nonsmokers, 15 light/moderate smokers, 12 heavy smokers, and 19 patients with carcinoma of the lung. Patients with carcinoma of the lung had marked depression in NK activity compared with nonsmokers. Light/moderate smokers had NK activity comparable to that of nonsmokers, whereas heavy smokers had marked depression in NK activity that was comparable to that of patients with carcinoma of the lung. These results suggest that smoking-induced alterations in NK activity may have a role in the pathogenesis of smoking-associated carcinoma of the lung.