Platelet-activating factor (PAF), a glycerophospholipid with proinflammatory properties, exerts its biological effects by interacting with the PAF receptor (PAFR) expressed on many different cell types. The PAFR specifically binds phosphorylcholine, the biologically active component of PAF. However, phosphorylcholine is also a component of the cell wall of nontypeable Haemophilus influenzae (NTHi). In recently published in vitro experiments, the invasion of respiratory epithelial cells by NTHi was mediated by the PAFR. To determine the role of the PAFR in host defense against pneumonia induced by NTHi, PAFR-deficient (PAFR-/-) and normal wild-type mice were intranasally inoculated with NTHi. The absence of a functional PAFR was associated with a normal innate immune response as indicated by similar bacterial counts, myeloperoxidase activity, and inflammation within the pulmonary compartment of PAFR-/- and wild-type mice. These data indicate that the PAFR does not interfere with the clearance of NTHi from the respiratory tract.