It has been previously shown that conventional methods of measuring the single-breath diffusing capacity of the lung for carbon monoxide (DLCOsb) overestimate diffusion in normal subjects when the expiratory flow rate is reduced, when the collection of the exhaled alveolar gas sample is delayed, and/or when too large an alveolar gas sample is collected. Conventional methods use a single breathholding equation to analyze the entire single-breath maneuver, which consists of inhalation, breathholding, and exhalation. We previously developed a method of calculating DLCOsb using 3 separate equations, one for each phase of the single-breath maneuver. Using this method, DLCOsb measurements are unaffected by changes in expiratory flow rate or by the size and timing of the alveolar gas sample, as these parameters are analytically included in the analysis. We hypothesized that in patients with air-flow obstruction, conventional methods of measuring DLCOsb would overestimate diffusion. We examined the effects of measuring DLCOsb using rapid inhalation and exhalation maneuvers in a group of normal subjects and in 3 groups of patients with emphysema, asthma, and cystic fibrosis, respectively. First, we found that, whereas conventional methods specify 750 ml or 1 L of gas to be used for dead space washout, the washout volumes, as measured from a continuous monitor of the helium concentration in the exhaled gas in the single-breath maneuver, exceeded 1 L in 26% of the study group.(ABSTRACT TRUNCATED AT 250 WORDS)