Computed tomography-guided percutaneous lung biopsy is a well-recognized procedure for obtaining tissue for diagnosis in adults with interstitial lung diseases. Recently this methodology has been extended to pediatric practice. We have further refined this technique by employing high-resolution computed tomography (HRCT) under general anesthesia to obtain maximum anatomical detail. High-quality images are obtained that accurately define the extent of disease, and percutaneous biopsies are then taken from a suitable area of radiological abnormality using an 18G Monopty needle. Twenty-six investigations have been performed on 24 patients. The diagnosis was established from 14 biopsies, and histological and/or radiological information that contributed to patient management was obtained from a further 4 procedures. In 4 patients the histological findings were inconclusive, and the final diagnosis was only confirmed by open lung biopsy and/or other investigations. The procedure was generally well tolerated, although chest drainage for pneumothorax was required in two patients. HRCT-guided percutaneous lung biopsy is a useful initial approach to the diagnosis of interstitial lung disease in selected patients; the necessity of more invasive procedures such as open, thoracoscopic, or transbronchial lung biopsy can thus generally be avoided.