The application of open-lung biopsy to a patient with diffuse pulmonary infiltrate is dependent on whether it affords to a specific information and leads to a change in therapy. To evaluate the impact of open-lung biopsy on diagnosis and treatment of diffuse pulmonary infiltrates, we conducted a retrospective review of 37 patients undergoing this procedure during a 8-year period. There were 26 males and 11 females, at an average age of 53 years (ranging from 3 months to 79 years). Diagnostic yield was 97.2%, and biopsy yielded a specific diagnosis in 25(67.6%) patients and a change in therapy in 19 (51.4%) patients. Complications developed in 4 (11%) patients and the rate was higher under local anesthesia (3/4). Seven patients died, but no one was related to biopsy procedure. A specific diagnosis was obtained in 4 (50%) of the 8 immunocompromised patients, and a change in therapy occurred in 2 (25%) of these patients after biopsy, but these findings could not affect the survival rates. A specific diagnosis was obtained in 21 (72.4%) of the 29 nonimmunocompromised patients and a change in therapy occurred in 17 (58.6%) patients in this group. Five (83%) of 6 patients, who lacked definite tissue diagnosis by transbronchial biopsy, achieved confirmed diagnosis by open-lung biopsy. Open-lung biopsy in patients with a diffuse pulmonary infiltrate is an accurate diagnostic tool and frequently leads to a change in treatment. The procedure can be performed with acceptable morbidity and mortality in nonimmunocompromised patients, but should be used conservatively in immunocompromised patients.