Epidermal growth factor is an important modulator of cell growth, and its role in normal wound healing is well documented. Epidermal growth factor receptors have been identified in tympanic membranes of different animals. The ability of epidermal growth factor to promote healing of tympanic membrane perforations has recently been shown in experimental animals. We performed a double-blind, placebo-controlled study of the effect of epidermal growth factor applied locally on the tympanic membrane for 1 week in patients with chronic perforations. Seventeen adult patients took part in the study, eight in the epidermal growth factor group and nine in the placebo group. Three placebo-treated patients were later treated with epidermal growth factor, and five patients received repeated epidermal growth factor treatment. Perforation size was measured as a percentage of the tympanic membrane area before and at least 1 month (mean, 2.6 months) after treatment. One perforation in the placebo group healed completely, but none of the epidermal growth factor-treated perforations closed. Perforations became slightly smaller in both groups (mean decrease, 0.3% and 2.7% for epidermal growth factor and placebo, respectively), but these changes in size were not statistically significant for either group. At otomicroscopy, a proliferation reaction with thickening of the tympanic membrane and pseudomembrane formation at the perforation edge could be seen in some ears. Histologically, a sample from one epidermal growth factor-treated ear demonstrated signs of hypertrophic epithelium when compared with the morphology of a placebo-treated tympanic membrane. The only complications were two mild infections in the placebo group. Hearing remained stable after epidermal growth factor treatment.