Platelet-activating factor (PAF) is a phospholipid with potent, diverse actions, which has been implicated as an important mediator in host defence against several intracellular pathogens. To determine the role of PAF in host defence in pulmonary tuberculosis, PAF receptor-deficient (PAFR-/-) and wild-type (PAFR+/+) mice were infected intranasally with a virulent strain of Mycobacterium tuberculosis. Mycobacterial outgrowth in lungs and liver did not differ significantly between PAFR-/- and PAFR+/+ mice at 2 or 6 weeks postinfection. After 28 weeks, 86% of PAFR-/- mice and 79% of PAFR+/+ mice had died (non-significant). In addition, both mouse strains were indistinguishable with respect to histopathology, the recruitment and activation of lymphocytes, and cytokine concentrations in the lung. These data suggest that PAF is not involved in the protective immune response to tuberculosis.