Background: Exhaled breath studies suggest that humans exhale fine particles during tidal breathing, but little is known of their physical origin in the respiratory system during health or disease. Methods: Particles generated by 3 healthy and 16 human rhinovirus (HRV)-infected subjects were counted using an optical particle counter with nominal diameter-size bins ranging between 0.3 and 10 mm. Data were collected from HRV-infected subjects during tidal breathing. In addition, data from healthy subjects were collected during coughs, swallows, tidal breathing, and breathing to total lung capacity (TLC) and residual volume (RV). Using general additive models, we graphed exhaled particle concentration versus airflow during exhalation. Exhaled particles were collected from expired air on gelatin filters and analyzed for HRV via quantitative PCR. Results: HRV-infected subjects exhaled from 0.1 to 7200 particles per liter of exhaled air during tidal breathing (geometric mean ¼ 32 part/L). A small fraction (24%) of subjects exhaled most (81%) of the particles measured and 82% of particles detected were 0.300-0.499 mm. Minute ventilation, maximum airflow during exhalation, and forced expiratory volume 1 second (FEV 1 % predicted) were positively correlated with particle production. No human rhinovirus was detected in exhaled breath samples. Three healthy subjects exhaled less than 100 particles per liter of exhaled air during tidal breathing and increased particle concentrations more with exhalation to RV than with coughing, swallowing, or rapid exhalation. Conclusions: Submicron particles were detected in the exhaled breath of healthy and HRV-infected subjects. Particle concentrations were correlated with airflow during the first half of exhalation, and peaked at the end of exhalation, indicating both lower and upper airways as particle sources. The effect of breathing maneuver suggested a major contribution from lower airways, probably the result of opening collapsed small airways and alveoli.