The single breath diffusing capacity of the lung for carbon monoxide (Dsb) was measured using three equations to describe CO uptake separately during inhalation, breath holding, and exhalation in 24 patients with cystic fibrosis and 30 control subjects with similar age and height distributions. Using the control group, we developed two prediction equations for Dsb: one based on height, age, and sex; and another based on alveolar lung volume (VA) to the 2/3 power. We also developed a prediction for Dsb/VA (Kco) based on height. The Dsb as percent predicted (% pred) using either prediction equation decreased with increasing age and height as well as with decreasing % pred maximal midexpiratory flow rate (FEF25-75) in cystic fibrosis patients but not in controls. The Kco (% pred) also decreased in cystic fibrosis with increasing age and decreasing percent pred FEF25-75. We conclude that in patients with cystic fibrosis, Dsb decreases with variables that relate to increasing disease severity (age, height, and increasing airflow obstruction).