Epistaxis from the anterior septum is frequently treated with a topical application of silver nitrate, which cauterizes the bleeding vessel. However, this treatment causes a septal perforation in a small percentage of patients. We report our study of the histologic effect of topical silver nitrate on samples of septal tissue obtained from 11 patients. We found that 30 seconds of exposure allowed silver nitrate to penetrate to a depth of approximately 1 mm. Longer exposure (45 and 60 sec) resulted in no significant additional penetration. Similarly, the amount of silver nitrate deposition into the chondrocytic lacunae did not vary significantly with the length of exposure. On the other hand, the depth of deposition into the extracellular matrix was positively associated with the duration of exposure. We found no direct evidence that silver nitrate exerted any damaging effect on septal cartilage. Instead, the development of septal perforations in patients who receive topical silver nitrate may be attributable to necrosis of the septal cartilage following damage to the overlying perichondrium, from which it derives its blood supply.