Inhalation of medicine for the treatment of lung and other diseases is becoming more and more a preferred option when compared to injection or oral intake. Unfortunately, existing devices such as the popular pressurized metered dose inhalers and dry powder inhalers have rather low deposition efficiencies and their drug-aerosol deliveries are non-directional. This is acceptable when the medicine is inexpensive and does not cause systemic side effects, as it may be the case for patients with mild asthma. However, the delivery of aggressive chemicals, or expensive insulin, vaccines and genetic material embedded in porous particles or droplets requires optimal targeting of such inhaled drug-aerosols to predetermined lung areas. The new methodology introduces the idea of a controlled air-particle stream which provides maximum, patient-specific drug-aerosol deposition based on optimal particle diameter and density, inhalation waveform, and particle-release position. The efficacy of the new methodology is demonstrated with experimentally validated computer simulations of two-phase flow in a human oral airway model with two different sets of tracheobronchial airways. Physical insight to the dynamics of the controlled air-particle stream is provided as well. (C) 2008 Elsevier Ltd. All rights reserved.