BACKGROUND: It is most physiologic to measure the diffusing capacity of the lung by using oxygen, but it is so difficult to measure partial pressure of oxygen in the capillary blood of the lung that in clinical practice it is measured by using carbon monoxide, and single-breath diffusing capacity method is used most widely. However, since the process of withholding the breath for 10 seconds after inspiration to the total lung capacity is very hard to practice for patients who suffer from cough, dyspnea, etc, the intrabreath lung diffusing capacity method which requires a single exhalation of low-flow rate without such process was devised. In this study, we want to know whether or not there is any significant difference in the diffusing capacity of the lung measured by the single-breath and intra-breath methods, and if any, which factors have any influence. METHODS: We chose randomly 73 persons without regarding specific disease, and after conducting 3 times the flow-volume curve test, we selected forced vital capacity(FVC), percent of predicted forced vital capacity, forced expiratory volume within 1 second(FEV1), percent of forced expiratory volume within 1 second, the ratio of forced expiratory volume within 1 second against forced vital capacity(FEV1/FVC) in test which the sum of FVC and FEV1 is biggest. We measured the diffusing capacity of the lung 3 times in each of the single-breath and intra-breath methods at intervals of 5 minutes, and we evaluated which factors have any influence on the difference of the diffusing capacity of the lung between two methods[the mean values(ml/min/mmHg) of difference between two diffusing capacity measured by two methods] by means of the linear regression method, and obtained the following results: RESULTS: 1) Intra-test reproducibility in the single-breath and intra-breath methods was excellent. 2) There was in general a good correlation between the diffusing capacity of the lung measured by a single-breath method and that measured by the intra-breath method, but there was a significant difference between values measured by both methods(l.0l+/-0.35ml/min/mmHg, p<0.01) 3) The differnce between the diffusing capacity of the lung measured by both methods was not correlated to FVC, but was correlated to FEV1, percent of FEV1, FEV1/FVC and the gradient of methane concentration which is an indicator of distribution of ventilation, and it was found as a result of the multiple regression test, that the effect of FEV1/FVC was most strong(r=-0.4725, p<0.01) 4) In a graphic view of the difference of diffusing capacity measured by single-breath and intra-breath method and FEV1/FVC, it was found that the former was divided into two groups in section where FEV1/FVC is 50~60%, and that there was no significant difference between two methods in the section where FEV1/FVC is equal or more than 60% (0.05 +/-0.24ml/min/mmHg, p>0.1), but there was significant difference in the section, less than 60%(-4.5+/-0.34ml/min/mmHg, p <0.01). 5. The diffusing capacity of the lung measured by the single-breath and intra-breath method was the same in value(24.3 +/-0.68ml/min/mmHg) within the normal range(2%/L) of the methane gas gradient, and there was no difference depending on the measuring method, but if the methane concentration gradients exceed 2%/L, the diffusing capacity of the lung measured by single-breath method became 15.0+/-0.44ml/min/mmHg, and that measured by intra-breath method, 11.9+/-0.5 1ml/min/mmHg, and there was a significant difference between them(p<0.01). CONCLUSION: Therefore, in case where FEV1/FVC was less than 60%, the diffusing capacity of the lung measured by intra-breath method represented significantly lower value than that by single-breath method, and it was presumed to be caused largely by a defect of ventilation- distribution, but the possibility could not be excluded that the diffusing capacity of the lung might be overestimated in the single-breath method, or the actual reduction of the diffusing capacity of the lung appeared more sensitively in the intra-brerath method.