To explain why the single-breath carbon monoxide diffusing capacity (Dsb) was, on the average, elevated in 163 asthmatic subjects and 175 patients with cystic fibrosis, we simulated this elevation in ten normal subjects by having them perform the test for Dsb through an inspiratory obstruction. This resulted in an 18 percent increase in Dsb corrected for pulmonary volume. Inhalation of a bronchodilator drug was associated with relief of obstruction and a fall in the corrected Dsb in 31 asthmatic subjects but did not change either the obstruction or the corrected Dsb in 17 patients with cystic fibrosis. We suggest that elevated Dsb in asthma and cystic fibrosis is partly due to maximal inspiration against obstructed airways. This requires abnormally negative intrathoracic pressures, increasing the pulmonary capillary blood volume, and, thereby, increasing the Dsb.