There is an urgent need for simple, inexpensive, noninvasive, and repeatable technique for the diagnosis of pulmonary diseases. Bronchoalveolar lavage, which is the gold standard diagnostic method for pulmonary diseases, does not meet any of these criteria. This study seeks to develop and optimize a novel technique of Internal Airway Percussion (IAP) to facilitate the collection and characterization of human respiratory system exhalates. The IAP device transmits sound waves into the respiratory tract, thereby increasing the release of aerosolized particles within exhaled breath by vibrating both lungs. Nine combinations of sound wave frequencies and amplitudes were studied to determine optimal frequency and amplitude combination for maximum aerosol particle gain in healthy human subjects. Square-shaped sound waves generated at 15 Hz and 3 cm H2O resulted in 15 times greater total mass of collected particles in the first 2 min of sampling, and 1.2 to 1.5 times increase in count median diameter of the particles. IAP, optimized at the frequency of 15 Hz and the pressure amplitude of 3 cm H2O, increased the total mass of particles exhaled from the human respiratory system. IAP has a broad range of potential clinical applications for noninvasive diagnosis of lung diseases including asthma, cystic fibrosis, pneumonia, and lung cancer, along with improvement of mucus clearance.