Female Sprague-Dawley rats were exposed to mainstream smoke from standard reference cigarettes and a nontobacco cellulose cigarette for 35 days. Whole smoke and smoke fractions were investigated. Lung inflammation was evaluated by differentiation of bronchoalveolar lavage cells and lymphocytes in thoracic lymph nodes. Histopathological changes in the nose and larynx were assessed. Results showed that the particulate phase of cigarette mainstream smoke is mostly responsible for inflammation in the lung (neutrophil increase up to 240-fold) and hyperplastic and metaplastic epithelial changes in the larynx, whereas irritative volatile constituents in the gas phase are mostly responsible for changes in the nose.