DLNO/DLCO directly measures the ratio of the diffusing capacities of the lung for nitric oxide (NO) and carbon monoxide (CO). In terms of the Roughton and Forster (1957) equation, 1/DL=1/Dm+1/θVc, where Dm is the membrane (Dm) and θVc is the red cell component of the overall diffusing conductance (DL); DLNO mostly reflects the Dm component and DLCO the θVc red cell component. The DLNO/DLCO ratio is positively related to the DmCO/Vc ratio and the CO red cell resistance (1/θCOVc) as a percentage of the total resistance (1/DLCO), independent of the absolute values of DLNO or DLCO. In clinical studies, a raised DLNO/DLCO ratio (≥110% predicted versus a control group), plus a low DLNO and DLCO (<67% pred), predicts pulmonary vascular disease, while a low DLNO/DLCO ratio, with similarly reduced DLNO and DLCO, is associated with interstitial lung disease with fibrosis. More clinical studies are needed, and reference values need to be better defined.