The presence of a resident population of intravascular macrophages in the sheep lung was investigated. Injection of fluorescent microspheres into the sheep results in uptake by a population of large phagocytic cells scattered within the alveolar capillaries of the lung. By contrast, the rat lung has no uptake of these fluorescent microspheres into the alveolar walls. The cells are large, extremely irregular in shape, often exceed 30 micron in length, and lie within the vascular lumen, apposed to the underlying endothelium. They have several features characteristic of mature macrophages including numerous pseudopodia, a partially preserved cell coat, wormlike bodies ("micropinocytosis vermiformis"), and numerous phagosomes that often contain erythrocytes. Unlike other species such as the rat, in which the mononuclear phagocyte system is distributed primarily in the liver and spleen, the sheep lung has a significant clearance function. Moreover, the presence of these cells in the lung may have important implications for studies of the inflammatory response to pulmonary vascular injury in the sheep.