Disruption of myelinated nerve fibers usually constitutes the most significant damage contributing to chronic neurologic deficits in severe spinal cord injuries. Inflammatory responses form one facet of a wide array of pathologic phenomena that combined to produce this damage. The therapeutic importance of inflammation is amplified by its delayed time-course and the number of different approaches that may be taken to its modulation. The response to trauma involves two significant waves of cellular infiltration: the first, dominated by polymorphonuclear leukocytes, peaks within a few hours; the second, by macrophages, begins after 1-2 days and reaches a peak at 5-7 days. Secondary demyelination of surviving nerve fibers and delayed loss of axons coincide with the macrophage response, and may be an example of "bystander damage" caused by the cytotoxic products of activated phagocytes. We know relatively few details of this delayed pathologic change, even in animal models. In particular, it is difficult to separate potential beneficial effects of macrophages in removing cellular debris, stimulating tissue revascularization and repair of the central nervous system environment, from the potential destructive effects associated with their phagocytic activity and their stimulation of scar formation through the release of factors that induce proliferation of peripheral cellular components within the injured spinal cord.