The aim of this study was to analyse the quality and diagnostic value of lung biopsies for the diagnosis of interstitial lung disease (ILD), taken with diathermy coagulation cup forceps during medical thoracoscopy. Patients with ILD, not specified after thorough clinical assessment, high-resolution CT (HRCT), bronchoalveolar lavage and transbronchial biopsy, were studied. Medical thoracoscopy was performed in an endoscopy suite under neuroleptic anaesthesia with spontaneous ventilation. Biopsy specimens were analysed prospectively by one lung pathologist blinded to the clinical findings. Over 2 yrs, 118 samples were analysed from 24 consecutive patients. A good quality biopsy was obtained in 23 patients, and 78% of the samples were of good quality. Biopsy findings plus clinical and HRCT data revealed a relevant diagnosis in 18 patients and some diagnostic clues in four patients, for whom further examinations were needed. No major complications occurred. Chest tube drainage averaged 5.3+/-4.7 days, and was related to the total lung capacity (p=0.008), which mirrors the severity of ILD. Separate sampling of biopsies from different lobes proved to be useful in one third of the cases. In conclusion, lung biopsy sampling can be performed safely by interventional pulmonary endoscopists and has a good diagnostic yield in interstitial lung disease of unknown origin.