Positron emission tomography (PET) was used to quantify 18fluorodeoxyglucose (18FDG) uptake in rabbits with experimental pneumonitis localized to the right upper lobe. In Streptococcus pneumoniae-induced pneumonia, which causes a profound inflammatory response lasting several days before it resolves, 18FDG uptake was pronounced at 15 h after the onset of inflammation, but by 48 h there was little uptake. In bleomycin injury, which progresses from an acute inflammatory stage to chronic inflammation and scarring, 18FDG uptake detectable by PET persisted for up to 21 d. Autoradiography of histologic sections after intravenous administration of [3H]deoxyglucose 15 h after streptococcal instillation and 2 wk after bleomycin instillation showed that, in both models, deoxyglucose uptake was localized to neutrophils. In the streptococcal model there was little 18FGD signal at 6 h, when major neutrophil migration occurs. At 15 h, [3H]deoxyglucose-labeled neutrophils were present in the airspaces but not in the alveolar septa, suggesting that the deoxyglucose signal reflected a postmigratory neutrophil event, probably the respiratory burst. Thus, PET of 18FDG uptake may provide a novel and readily repeatable, noninvasive approach to the in vivo study of neutrophil activity at otherwise inaccessible sites.