Comparison of methods of aerosol generation and inhalation is required to improve standardization of inhalation provocation tests. We compared two widely used methods in 10 asthmatics, by measuring the dose and distribution of radiolabeled aerosol deposited in the throat and lung, and the provocation concentration of inhaled histamine required to reduce the FEV1 by 20% (PC20). In one method, aerosol was generated by a DeVilbiss 646 nebulizer attached to a dosimeter, and was inhaled by 5 inspiratory capacity breaths. The measurements with each method were repeated once to determine the reproducibility of results. Both methods deposited the same dose in the lung, but the distribution of the dose was different; the dosimeter method deposited more aerosol in the throat and central airways. The PC20 obtained with each method was the same. The reproducibility of all measurements in the same subject was similar. The lung dose deposited by each method in different subjects varied to the same degree. The results indicated that the bronchial response to inhaled histamine can be measured as reliably using a nebulizer and tidal breathing as by a more complex dose-metering device. They also suggested that, when the methods are regulated as described, the PC20 will have the same clinical significance.