Because lung nitric oxide (NO) diffusing capacity (DL) represents alveolar-capillary gas diffusion, we queried as to whether disturbances of pulmonary gas exchange in interstitial lung disease (ILD) are appropriately reflected by using NO. In this pilot study, we applied the (15)N-labeled stable isotope (15)NO (relative abundance 0.37% of total NO) in order to ignore the endogenous NO production. In 10 ILD-outpatients, we measured DL (15)NO by performing the single-breath method. Lung function parameters as well as arterial oxygen partial pressure (PaO(2)) were also tested. Values of DL (15)NO ranged within 50-151 ml (15)NO/(mmHg min). Ratios of DL (15)NO/reference were between 43 and 108% of predicted data as taken from our previous work on healthy volunteers [Eur. J. Physiol. 446 (2003) 256]. We found a significant reduction of DL (15)NO/reference in five patients. Additionally, values of PaO(2) were significantly correlated to ratios of DL (15)NO/reference (adjusted R2 +/-SEE=0.407+/-8.051). In conclusion, (15)NO represents an appropriate indicator gas for reflecting an ILD-induced impairment of alveolar-capillary gas exchange.