Large tympanic membrane perforations usually require a surgical tympanoplasty for closure. Reducing surgical costs and risks has encouraged investigators to examine nonsurgical office procedures for healing these perforations. Growth accelerators are the most promising agents. We study here the closure of large acute perforations using weekly applications of 1 mg of 1% hyaluronic acid (HA), 0.4 microg basic fibroblast growth factor (bFGF), or 1.0 microg epidermal growth factor (EGF) directly to the tympanic membranes of the experimental ears. Control ears were treated with 0. 1 mL Vasocidin. Complete closure was obtained in 100% of the ears treated with HA and EGF and 85.7% of those treated with bFGF by day 21, compared with 63.6% of the controls by day 32. Moderate-to-severe ipsilateral and contralateral external canal hypertrophy was noted in 14.2% and 37.5% of the ears treated with bFGF and HA, respectively, but was not seen in ears treated with EGF or in the control group.