This study prospectively compared the diagnostic yield of transbronchial biopsies using large and small forceps (cup sizes, 3 x 2 x 0.9 versus 2 x 1.5 x 0.6 mm, respectively). Diagnostic yield was compared by a pathologist, blinded to the size of forceps used on the basis of the relative amount of tissue obtained, alveolar tissue obtained, and ability to ascertain a histopathologic diagnosis. Large forceps obtained significantly more tissue than did small forceps (20 of 27 patients [74%] versus five of 27 patients [19%], p < 0.005, with similar amounts obtained in two patients). Also, large forceps obtained significantly more alveolar tissue than did small forceps (16 of 22 patients [73%] versus six of 22 patients [27%], p < 0.05, with no alveolar tissue obtained in five patients). In 18 of the 27 patients, biopsies performed resulted in nonspecific diagnoses, including fibrosis or chronic inflammation. All nine of the patients with a specific diagnosis were ultimately proved to have sarcoidosis. There was a trend toward more of these patients having noncaseating granulomas obtained with the large forceps than with the small forceps (seven of nine patients versus four of nine patients). No difference was observed in the amount of postbiopsy bleeding with either forceps. We conclude that large forceps used for transbronchial biopsy yield more tissue and more alveolar tissue than do small forceps. These findings may have an impact on the diagnostic yield in some diseases such as sarcoidosis.