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Hypothesis: The aims of the present study were to determine the effect of epidermal growth factor (EGF) and pentoxifylline on subacute tympanic membrane (TM) perforations and to quantify the healing rate of such perforations treated with these drugs alone or in combination. Background: It is known that EGF modulates in vitro and in vivo proliferation of epithelial and endothelial cells. Pentoxifylline is a methylxanthine that has been used to treat experimental skin flaps and venous leg ulcers. Data in the literature regarding this subject are contradictory, and quantitative data regarding the effects of EGF and pentoxifylline on TM perforation healing are scarce. Methods: We studied 50 chinchillas submitted to TM perforation. On postoperative Day 30, eight were selected for histologic analysis. Of the remaining 42, those presenting little or no healing were distributed into four groups: control, EGF, pentoxifylline, and EGF combined with pentoxifylline. Results: Histologic analysis showed that the observation period adopted was sufficient to consider the TM perforations subacute. We found significant differences between the study groups and the control group in the healing rate of subacute TM perforations during a 30-day period (analysis of variance; p G 0.001), which was 30.3% for the EGF group, 3.6% for the pentoxifylline group, 16.5% for the EGF-pentoxifylline group, and 8.7% for the control group. Conclusion: The use of EGF promoted healing of subacute TM perforations in chinchillas, and the use of pentoxifylline did not. The combination of the two had no synergistic effect on the healing of these perforations. Key Words: ChinchillaVEpidermal growth factorVMiddle earVPentoxifyllineVTympanoplastyVWound healing. Otol Neurotol 27:720Y727, 2006.