CAL remains an important cause of morbidity and mortality. The diffusing capacity has ranked high in the assessment of CAL because it represents the best pulmonary function test to assess the integrity of the pulmonary capillary bed. Unfortunately, numerous physiologic, pathologic, and technical factors affect the test, thus limiting its sensitivity and specificity. HRCT techniques offer the potential to assess the extent of emphysema more accurately, but the technique requires greater standardization and is more expensive and less noninvasive than DLcoSB testing. Although the CIBA symposium considered DLcoSB "essential" in the investigation of the CAL patient, 16 the use of conventional DLcoSB testing in the seated position at rest is not currently advised as a routine screening procedure. The test must be performed in a center with high degree of quality control, and the results can be of value only by integrating the result into a comprehensive clinical assessment. Within this context, conventional DLcoSB testing may provide limited information about the extent of emphysema because reductions in DLcoSB correlate with the extent of emphysema by HRCT. When DLcoSB is normal, it may point in the direction of considering asthma as the cause of the airflow limitation. It may also provide information about disease severity and prognosis in O2-dependent CAL patients. The test should be a part of the investigation of the patient with unexplained dyspnea. It remains controversial how emphysema correlates with the degree of impairment in CAL, and further work needs to be done to clarify this relationship. This requires a reexamination of current CT methods 110 and the relationship between DLcoSB, structural changes in the lung, and HRCT evidence of emphysema. Refinements in DLcoSB testing methods, such as the measurement of DLcoSB-3EQ are linked to rapidly responding CO analyzers and computer-driven software, which will potentially improve the accuracy and reproducibility of the test, particularly in the presence of airway obstruction and nonuniform distribution of ventilation. Such refinements, which offer the possibility that tests of diffusion could become more useful markers of disease, include measuring DLcoSB when the pulmonary capillary recruitment is near maximal (head-down position, exercise), enhancing the sensitivity of the test to alterations in the lung periphery, standardizing previous volume history, developing more precise corrections for Hb and COHb, and developing an index of diffusion nonuniformity.