18F-fluorodeoxyglucose (18FDG) uptake measured by positron emission tomography (PET) allows assessment of neutrophil activity in vivo and is increased in patients with airway inflammation or infection. Because infection but not rejection elicits a highly neutrophilic response, we assessed the ability of this non-invasive technique to differentiate these two events in lung transplant recipients. 18FDG-PET was measured in 15 patients classified by clinical, radiologic, and pathologic criteria. 18FDG-PET signal was increased with proven infection but not when no infection was identified (mean [standard error of mean]: 8.00 [1.81] and 3.16 [0.61], respectively [P = 0.021]. Rejection alone did not increase the signal. These data confirm that neutrophil activation is not a feature of acute rejection and indicate that a high 18FDG-PET signal is indicative of infection but not rejection in lung transplant recipients. This non-invasive and repeatable test could reduce the number of transbronchial biopsies required during episodes of breathlessness after lung transplantation.