Rapidly progressive pulmonary distress occurs as a secondary complication in immunocompromised pediatric patients. These patients usually develop a pattern of diffuse alveolar and/or interstitial infiltrates on chest x-ray and pursue a rapidly downhill course despite intensive respiratory support with the use of multiple and varied antimicrobial regimens. These patients are subjected to diagnostic open lung biopsies to establish a diagnosis. The diagnostic value of open lung biopsy and its current impact on therapy is not clearly established. This retrospective study attempts to determine the impact of open lung biopsy on diagnosis and therapeutic outcome. Between November, 1974, and October, 1982, 40 diagnostic open lung biopsies were performed on immunocompromised patients with clinically progressive respiratory disease. Adequate follow-up for complete evaluation was possible in 34 of these patients. Most of these patients had hematologic malignancies and all were on chemotherapeutic drugs at time of open lung biopsy. Open lung biopsy was considered helpful, ie, resulted in a change in antimicrobial therapy or substantiated preoperative therapy, in 17 of our 34 patients (50%). A "treatable" condition, amenable to antimicrobial therapy, was diagnosed in 16 of our patients (47%). Pneumocystis carinii pneumonitis (PCP) was the most common diagnosis in 11 (69%) of our "treatable" patients. The remaining five "treatable" patients had sarcoidosis (1), histiocytosis X (1), bacterial pneumonitis (1) and fungal pneumonitis (2). No diagnosis was achieved by open lung biopsy in ten (30%) of our patients. There were two complications attributable to open lung biopsy (6%), including one death. All PCP patients treated with trimethoprim sulfamethoxazole (T/S) survived.(ABSTRACT TRUNCATED AT 250 WORDS)