This chapter focuses on the host immune response to mycoplasma respiratory infection. M. pneumoniae is often grouped with Chlamydia pneumoniae and Legionella species as bacterial causes of "atypical" community-acquired respiratory infections. The pathogenicity of M. pneumoniae is dependent on its extracellular attachment and the initiation of host cell membrane injury. M. pneumoniae causes physiologic and cytolytic injury to the host cells in part by the production of hydrogen peroxide. Experimental findings suggest important mechanistic links between the pathogenesis of asthma and M. pneumoniae. In direct connection to human asthma, it was found that chronic asthmatics with evidence of respiratory M. pneumoniae infection by PCR had greater numbers of infiltrating mast cells in bronchial biopsies than asthmatics with negative M.pneumoniae PCR. M. pneumonia infection can result in increased expression of M. pneumoniae- specific IgE-this offers another route that infection by this organism could activate mast cells. Furthermore, the pattern of cytokine expression found in mast cells directly activated by M. pneumoniae has a TH2 bias. © 2005 Elsevier Inc. All rights reserved.