Apoptosis, or programmed cell death, is a critical regulatory mechanism involved in the function, homeostasis and stimulus response of many organ systems. In the middle ear, apoptosis could participate in mucosal remodeling or leukocyte clearance during otitis media (OM). Fas is a death receptor that can contribute to apoptosis in a variety of cell types. To assess the role of Fas signaling in OM, we probed for expression of Fas and Fas ligand (FasL) by polymerase chain reaction (PCR) during bacterial OM in the rat. In addition, we assessed the response of the middle ear to endotoxin, an inflammatory bacterial product that has been used as a model for otitis media in the mouse, in normal and Fas deficient mice. We saw evidence of increased expression of Fas and Fas ligand during bacterial OM. Moreover, the intensity of the mucosal response to endotoxin was significantly greater and the resolution of the response was prolonged in Fas deficient mice. Prolonged resolution of mucosal hyperplasia may reflect reduced apoptosis of the hyperplastic mucosal cells. Elucidation of the pathways that regulate the mucosal hyperplastic response during otitis media brings us closer to manipulating them in the interest of reducing the chronic complications of this disease.