Because of the high mortality associated with a diagnostic open lung biopsy in patients on mechanical ventilatory support, the clinical benefits of this procedure remain controversial. To assess the surgical results and the usefulness of open lung biopsies performed in this subset of patients, the clinical records of 27 patients who underwent open lung biopsy between January, 1987 and December, 1992 were reviewed. All patients were intubated for respiratory failure of unknown origin and were treated with antibiotics and/or steroids prior to the open lung biopsy. There were 13 men and 14 women with the mean age of 51 +/- 4.7 years (3 mos. to 82 years). The average duration for ventilatory support was 9 +/- 3.7 days (1 to 98 days). Nonoperative invasive diagnostic procedures were performed in 19 patients (70%). The operative approach for biopsy was an anterolateral thoracotomy using a linear stapler: right in 10 patients (37%), left in 17 (63%). A specific histologic diagnosis with open lung biopsy was established in all patients. Based on the biopsy findings, a change in treatment was unnecessary in 9 patients (33%), the dose of corticosteroids was increased in 7 (26%), the corticosteroids were initiated in 6 (22%), and a new antibiotic was added in 5 (19%). Perioperative complications occurred in 11 patients (40%). Prolonged air leak was the most common complication (6/11 patients). Fourteen patients (52%) died within 30 days of the biopsy procedure.(ABSTRACT TRUNCATED AT 250 WORDS)