The dynamics of tissue macrophages are poorly understood. We have developed a model where only lung macrophages express high levels of enhanced green fluorescent protein (EGFP) and are easily identified and followed by confocal microscopy. The EGFP(+) cells had the morphology of macrophages and express CD11c, CD11b, and F4/80, but not NK1.1 or CD3. The F4/80(+)EGFP(+) cells were found exclusively in the lung and not in lymph nodes, spleen, blood, liver, intestine, or Uterus. These EGFP+ cells are phagocytic and can be activated to migrate within the lung in response to LPS stimulation. In this study, we describe a new model system that allows the specific study of macrophages in the lung. (c) 2005 Elsevier Inc. All lights reserved.