Invasive carcinoma of the larynx was induced in 36.8% of inbred Syrian golden hamsters from strain B10 15.16, susceptible to this type of cancer when exposed to smoke from reference filter cigarettes for 59-80 weeks. Nearly half the animals (47.4%) showed laryngeal cancer, including noninvasive carcinoma and carcinoma in situ, which occurred with daily smoke exposures (twice a day for 12 min each time, for 27 sec out of each min) 7 days a week at smoke concentrations of 22%. When the smoke concentration was reduced to 11%, the number of induced lesions was reduced proprotionately. When a portion of tobacco was replaced in the cigarettes by a tobacco supplement, Cytrel (a trademark of the Celanese Corp., Charlotte, N.C.), a reduction of carcinogenesis proportionate to the Cytrel content of the cigarette took place. Smoke from cigarettes containing only Cytrel and no tobacco induced no carcinomas under the conditions used. Other dose-related changes observed were laryngeal papillomas, laryngeal epithelial hyperplasia, tracheal epithelial hyperplasia, and metaplasia and accumulation of alveolar macrophages. Tar deposition in lungs and accumulation of alveolar macrophages. Tar deposition in lungs and larynges was determined in a separate study by means of a marker, decachlorobiphenyl, added to the cigarettes. Admixture of Cytrel to cigarettes reduced tar deposition in the respiratory tract, which paralleled the decrease in the incidence of laryngeal carcinoma. However, the amounts of tar deposited in the larynx when 100% Cytrel was smoked were still significant, even though no carcinomas were observed. Thus smoke from Cytrel tobacco supplement may be less carcinogenic than equal amounts of tobacco smoke.