Little is known about the arrested healing of chronic central tympanic membrane perforations and the mechanism involved in this process. Some authors have traced the failure to a growth factor deficiency at the perforation margin. In addition, recently, several growth factors have been tried out to improve tympanic membrane (TM) closure in animals. The authors sought to determine the expression of some well-known growth factor peptides in normal human TM and in TMs with a chronic central perforation.Total TM specimens were obtained from patients with a normal TM (N = 10) soon after death and from patients with a chronic perforation (N = 20) undergoing myringoplasty with use of an allograft TM. Formaldehyde solution-fixed TMs were analyzed after immunohistochemical staining using highly purified monoclonal antibodies to determine whether epidermal growth factor receptor (EGF-r), transforming growth factor-alpha (TGF-alpha), basic fibroblast growth factor (b-FGF), or transforming growth factor-beta 1 (TGF-beta 1) was expressed in the TMs.The distribution pattern for EGF-r, TGF-alpha, and b-FGF was similar in perforated and nonperforated TMs. In contrast to this, TGF-beta 1 staining was markedly different in perforated and nonperforated TMs. No or minimal TGF-beta 1 was observed in normal TMs, whereas TGF-beta 1 staining was prominent in perforated membranes, mostly at the perforation border.The authors experimental findings imply that EGF-r, b-FGF, and TGF-alpha expression are not significantly different in TMs with and without a central chronic perforation. However, for TGF-beta 1, the authors found an increased staining pattern in perforated TMs when compared with that of normal TMs, and staining at the fibrotic and scarred perforation margin was pronounced. Based on these findings, the authors speculate on the possible role of TGF-beta 1 in the development of the fibrotic scar at the perforation margin explaining the deficient healing pattern of tympanic membranes in chronic otitis media. Possible clinical implications for the future, including growth factor therapy, are discussed.