Open lung biopsy (OLB) is an important diagnostic tool in children with immune deficiency and/or chronic lung disease with diffuse pulmonary compromise. These patients require a tailored therapeutic approach owing to their fragile status and the side effects of unnecessary or inadequate treatment. Twenty-six patients of mean age 5.6 y underwent 41 open lung biopsies in our centre between 1991 and 1995. Seventeen (65%) were immunocompromised (including 13 with malignancy) and 9 had other lung diseases. The biopsies were diagnostic in 25 patients (96%), and complete clinical-pathological correlation was found in 11 (42%). A specific infectious aetiology was detected in nine patients (35%), all of them immunocompromised. Therapeutic changes were instituted on the basis of the biopsy findings in 18 patients (69%). Two patients had postoperative complications (prolonged pleural leak). We conclude that OLB is a safe diagnostic procedure even in the critically ill child and should be employed without hesitation when conventional methods fail to provide a definitive diagnosis to help redirect therapy.