Using a cell-isolation and -culture procedure specific for macrophages, we report the existence of giant (more than 50 microm diameter), multinucleated macrophages within an acute, 5-day-old adult rat spinal cord injury. The size and multinuclearity of these isolated giant cells was confirmed using transmission electron microscopy. Giant macrophages are markers for long-term infection, disease, and chronic injury in other soft tissues and are unexpected in the acute inflammatory stage of central nervous system injury. To our knowledge, this descriptive report is the first confirming the existence of giant macrophages in any injured nervous tissue, with additional data suggesting some of these cells to be multinucleated.