The diffusing capacity of the lung for carbon monoxide (DLco) is usually measured by the single breath method with a 10-second breath hold. With the introduction of rapid gas analyzers, an alternative method for measurement of DLco, the intrabreath method, has been developed. The intrabreath method does not depend upon length of time or other conditions during either breath holding or expiration. The aim of this study was to compare the single breath method and intrabreath method of DLco measurement. DLco measured by the intrabreath method (DLco IB) was compared with DLco measured by the single breath method (DLco SB) in 32 normal subjects, 88 patients with obstructive impairment and 39 patients with restrictive impairment. DLco SB could not be measured in 2 patients with obstructive impairment and 7 patients with restrictive impairment, while in all except one patient with severe restrictive impairment, DLco IB was able to be measured. There was an excellent correlation between DLco IB and DLco SB in normal subjects (rho = 0.942, p < 0.0001). There was no difference in the mean value between DLco IB (21.0 +/- 5.4 ml/min/mmHg) and DLco SB (20.9 +/- 4.9 ml/min/mmHg). In the obstructive impairment group there was also an excellent correlation between DLco IB and DLco SB (rho = 0.922, p < 0.0001). In the mild or moderate obstructive impairment group (%FEV1 > 50%), no difference between DLco IB (11.8 +/- 5.80 ml/min/mmHg) and DLco SB (12.4 +/- 4.68 ml/min/mmHg) was found. In the severe obstructive impairment group (%FEV1 < 50%), the DLco IB (7.29 +/- 3.61 ml/min/mmHg) was lower than the DLco SB (8.58 +/- 3.24 ml/min/mmHg) (p < 0.0001). The relation between DLco SB and DLco IB was equally strong in patients with restrictive impairment (rho = 0.742, p < 0.0001). There was an excellent correlation between DLco IB and DLco SB in normal subjects, the obstructive impairment group and the restrictive impairment group. The intrabreath method therefore seems to be a useful and reliable alternative to the single breath method for clinical measurement of DLco.