Evaluation of mediastinal masses often involves an array of imaging procedures and percutaneous biopsy techniques. Despite this, surgical intervention with an open biopsy is often required, especially to diagnose mediastinal malignancies. We report 22 patients with mediastinal masses who were managed with thoracoscopic biopsy, as opposed to open biopsy. All of these patients either had unsuccessful fine-needle aspiration or were unacceptable candidates for percutaneous aspiration. The patients ranged in age from 11 months to 67 years with a mean age of 17.2 +/- 3.6 years. Thoracoscopy provided an accurate tissue diagnosis in 19 of the 22 patients (86%) without need for an open diagnostic procedure. In 1 patient, histoplasmosis was suspected from the thoracoscopic biopsy, but open thoracotomy was needed for confirmation. Of the 19 patients with a positive tissue diagnosis, 3 patients had bronchogenic cysts that were completely resected by thoracoscopy. The mean duration of chest tube drainage was 2.3 +/- 0.2 days, and there were no complications or procedure-related deaths. The average length of hospitalization was 6.0 +/- 0.8 days. We believe that thoracoscopy is a safe, rapid, and effective modality for the diagnosis of mediastinal masses. Accurate tissue diagnoses are obtained in most patients without the need for additional procedures. In addition, we have demonstrated that complete excision of certain benign lesions during thoracoscopy is possible.