Three protocols have been devised for measuring nonspecific hyperresponsiveness using either histamine or methacholine as the stimuli: Chai Method, Cockcroft Method, and Yan Method. The first is a dosimeter method using incremental, cumulative doubling doses of methacholine or histamine. The second method uses the same doubling dosage regimen of histamine and methacholine and generates the aerosol using a Wright's nebulizer primed with 5 milliliter test solution and an oxygen flow rate of 7 liter/minute. The third method is a rapid, simple method which uses a hand held De Vilbiss nebulizer primed with saline or histamine. Several studies have compared responsiveness to histamine and methacholine, intrasubject day to day variability, and techniques of aerosol generation. A variety of different bronchial provocation methods have been described to test for specific bronchial hyperresponsiveness. Two methods which have been widely used are the dosimeter method and the tidal breathing method. In the dosimeter method the allergen is delivered via a dosimeter to deliver known amounts of allergen during each inspiratory maneuver. In the tidal breathing method the allergen is expressed from a continuous output nebulizer primed with a fixed volume of allergen solution and delivered via a 500 milliliter rebreathing bag linked to an oronasal mask for fixed time periods. An occupation method, in which the individual's work situation is simulated as closely as possible within a challenge chamber, and a new method for conducting specific inhalation challenges with occupational allergens in particulate form were also described.