The functional assessment of the response to bronchodilators in 2- to 5-year-old asthmatic children is technically difficult. For this reason, there have been no reports on the effects of long-acting bronchodilators, such as salmeterol, in this age group. Of the several techniques available for measuring resistance to airflow, forced oscillation remains the most adaptable to young children and the most practical for research and clinical use. In this stud we used the Jaeger MasterScreen Impulse Oscillometry System to assess the response of 2 to 5 year-old asthmatic children to an inhaled long-acting bronchodilator, salmeterol, by comparing it to the effect of a standard dose of the short-acting bronchodilator, albuterol. We performed a placebo-controlled, randomized, crossover study in 10 children aged 2 to 5 years who had a history of physician-diagnosed asthma and who were not on regular controller therapy. At weekly intervals after baseline measurements of reversibility, each child received two inhalations from an albuterol metered-dose inhaler (MDI) with a spacer (200 microg), or placebo MDI with spacer, or two inhalations from a salmeterol MDI (50 microg), or 50 microg from a salmeterol Diskus. Measurements were obtained at 5, 30, 60, 360, and 540 min, the last time interval only on the salmeterol days. Based on previous studies, total respiratory system reactance at 5 Hz (X5), calculated by the MasterScreen computer from mouth pressure and flow data, was used as the primary efficacy variable. The mean intra-individual variability in X5 was 10.5% (range 3.6% to 17.9%). The mean (SE) changes from baseline X5 at each time point were as follows: for placebo, 9.6 (3.0), 10.1 (2.6), 5.1 (2.9), 6.1 (3.5), p=0.36 vs. baseline; after treatment with albuterol, 32.7 (3.8), 53.9 (1.2), 47.3 (5.4), 18.1 (5.8), p<0.01 vs. baseline at all time points; after salmeterol MDI, 16 (6.4), 28.9 (5.2), 32.7 (3.9), 34.6 (4.4), 31.2 (4.8), p<0.05 at 60, 360, and 540 min; and after salmeterol Diskus, 16.4 (4.0), 16.9 (6.6), 27.8 (5.9), 28.6 (5.6), 33.8 (4.0), p<0.05 at 540 min. No significant adverse events or electrocardiographic changes were noted at any time. Impulse oscillometry is an acceptable method of assessing airway responses to bronchoactive drugs in this age group. Compared to albuterol and to its effect in older children and adults, the response to salmeterol Diskus appears to be somewhat blunted in this age group. The MasterScreen system is well suitedfor pharmacodynamic studies and clinical investigations in pre-school-aged children.