Cigarette smoking is the major contributor to chronic bronchial irritation, and tobacco smoke is the most common bronchial carcinogen. A newly developed quantitative sputum cytology test was applied to three-day-pooled, spontaneously produced sputa collected from 349 cigarette smokers and 93 patients who had never smoked; the samples were processed by the Saccomanno technique. In addition to identifying malignant and precancerous cells in sputum, this test identifies eight morphologic parameters of bronchial irritation. Cross-sectional analysis of the cytologic data indicated that, within a 99% confidence interval, cigarette smokers had statistically significantly higher levels of all eight components, producing a unique profile. Discriminant analysis revealed that pigmentation of macrophages, alveolar macrophages and mucous spirals (in that order) were the leading components differentiating smokers from nonsmokers. This new quantitative sputum cytology test correlates with the model of lung carcinogenesis. The detection of proliferative cellular alterations, such as benign and early atypical metaplasia, represent the detection of chronic persistent irritation, which is considered to be a reversible change. The ability to monitor individual responses to toxic inhalants (before the development of irreversible disease) by utilizing a noninvasive test represents a unique opportunity to impact the historic course of lung carcinogenesis.