Sprague-Dawley rats were exposed nose-only for 1 h/day on weekdays for 13 weeks to the smoke from test and reference cigarettes. The test cigarette was a new prototype: the tobacco is heated rather than burned. The University of Kentucky lR4F cigarette was used as a reference. The exposures used were around 25% higher than those used in earlier studies, and for the test cigarette the resulting blood carboxyhemoglobin concentrations approached those associated with death (62 + %). The smoke from the reference cigarette produced substantial reductions in breathing frequency, whereas the smoke from the test cigarette did not. The availability of nicotine from test and reference cigarettes was very similar. The histopathology seen (mucus-secreting cells; nasal, laryngeal, and bronchial hyperplasia and squamous metaplasia, pulmonary macrophages) indicated that most of the changes observed in the reference animals were absent in the test animals. When changes were seen in the test groups (primarily in the larynx), they were substantially reduced when compared with the reference groups and were completely reversible.The authors thank