The measurement of bronchial hyperresponsiveness with inhaled aerosols is now accepted as an objective measurement of the severity of asthma. The most commonly used agents administered as aerosols are methacholine and histamine, which are believed to cause airways to narrow by contracting bronchial smooth muscle via specific receptors. Patients with asthma may also have an attack provoked by inhaling aerosols that increase or decrease the osmolarity of the fluid lining the airways. There is evidence to suggest that a change in the osmolarity of the airways causes the release of mediators from inflammatory cells in the airways. Thus, inhalational challenge with nonisotonic aerosols, such as water and hyperosmolar saline, may be useful to assess bronchial hyperresponsiveness to endogenously released mediators. Described in this article are some of the techniques used to challenge with nonisotonic aerosols, and airway responses are discussed in relation to responses obtained with other bronchial provocation tests. The mechanisms whereby these aerosols cause airways to narrow are considered, and the clinical implications of identifying responsiveness to these aerosols are discussed. Specific recommendations are made with respect to equipment, technique, and choice of aerosol.