2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) is a promising imaging procedure for detecting primary and metastatic cancer in the lungs. We have, however, failed to detect some small tumors in the lower lobes of the lungs. This study aimed to determine whether increase 18F background activity in the dependent lower lungs is present, which could make lesion detection more difficult. We measured the standardized uptake values (SUVs) for FDG of normal lung remote from the nodular lesion in 16 patients with newly diagnosed untreated lung lesions strongly suspected to represent non-small cell lung cancers. In addition, 15 patients with known or suspected primary breast cancers without pulmonary lesions were included as control subjects. After PET transmission images of the thorax were obtained, approximately 370 MBq of FDG was injected intravenously and imaging was immediately begun. Patients were supine throughout the study. SUVs were determined with images obtained 50-70 min after FDG injection. Regions of interest (ROIs) of 6x6 pixels were positioned over normal lung in anterior, mid, and posterior portions of upper, middle, and lower lung fields. Thus, as many as 18 ROIs were positioned in each patient. The SUVs of the posterior portion were significantly higher than those of the anterior and mid portions in the population of 31 cases (P <0.001). Also, the mean SUV of the lower lung field was significantly higher than the SUVs of the upper and middle lung fields in this population (P <0.01). This pattern was seen among the two groups of 16 patients suspected of having lung cancer and 15 control subjects. Background 18F activity was highest in posterior and lower lung in these patients. The maximum value of mean SUV observed in normal posterior lower lung was 0.804+/-0.230 (41% greater than the mean SUV in the anterior upper lung), which is in the range of the apparent SUV for a 5-mm lung lesion, with higher SUV, due to recovery coefficient issues. Thus this phenomenon could contribute to occasional false-negative lesions in those areas. Increased blood flow and FDG delivery and also scatter from heart and liver may contribute to the increased lower lung background activity. Regional differences in normal lung FDG uptake are significant and should be considered when interpreting pulmonary PET studies in patients with suspected primary or metastatic lung cancer.