Traumatic brain injury (TBI) induces inflammatory reactions, and one of the essential mediators of this reaction is nitric oxide (NO). The action of this compound is still under study because no clear consensus has been reached about its exact action in the central nervous system. Further, it is unknown if, in the damaged brain, its neuroprotective activity outweighs its putative neurodegenerative properties. Using ferrous-diethyldithiocarbamate chelate, a lipophilic spin trap for NO detection by electron paramagnetic resonance (EPR) spectroscopy, we followed NO production in injured brain of mature Wistar rats. To relate changes in the amount of NO in the lesioned brain to the activity of NO synthase (NOS), this study also used NADPH-diaphorase staining. Our data show a rapid drop of NO concentration in the damaged brain below control values. This phenomenon persisted over several hours postinjury and varied with brain region. This decrease in NO concentration was accompanied by a simultaneous increase in the number of NADPH-diaphorase-positive cells, perhaps indicative of increased NOS activity. It is therefore assumed that, in the lesioned brain, a very rapid removal of NO occurs via its transformation to other reactive species such as peroxynitrite, which further adversely influence the damaged tissue.