One hundred two 2-month-old male Syrian hamsters received 12 weekly sc injections of 0.25 mg diethylnitrosamine (DEN). Half the animals were also exposed for 10 minutes to cigarette smoke in Hamburg II-type smoking machines, three times per day, 5 days per week, for their life-span. The other half received sham exposure. Two additional groups of 51 hamsters each, serving as controls, received either only smoke or sham smoke exposures. The DEN treatment resulted in a significant increase (P less than 0.01) in epithelial lesions of the larynx, including laryngeal papillomas. Cigarette smoke inhalation had a significant (P less than 0.01) potentiating effect on the incidence of these lesions. We did not observe the high incidence of tumors of the nasal cavity, trachea, and the lower respiratory tract, or a significant development of malignant tumors, reported by several other investigators. The life-spans of the animals were unaffected by DEN and significantly increased (P less than 0.01) by exposure to smoke. The smoke-exposed groups had significantly lower mean body weights than their sham smoke-exposed cohorts.