1. Focal cortical freezing lesions in rats caused a widespread decrease in local cerebral glucose utilization (LCGU) in cortical areas of the lesioned hemisphere and this was interpreted as reflecting a depression of cortical activity (Pappius 1981). Cortical serotonin (5-HT) metabolism was increased throughout the lesioned hemisphere (Pappius and Dadoun 1987). To find if these changes in the serotonergic system are of functional importance and mediate the observed changes in LCGU, the effects of inhibition of 5-HT synthesis with p-chlorophenylalanine (PCPA) on cerebral metabolism and indoleamine content in injured brain were studied (Pappius et al. 1988). PCPA decreased 5-HT levels in the cortical and raphe areas of both intact and injured brain in a dose dependent manner. At doses of PCPA ineffective on LCGU (50 and 100 mg/kg) brain trauma still resulted in increased 5-HT metabolism. PCPA at doses which selectively ameliorated the depression of cortical LCGU in the lesioned hemisphere (200 and 300 mg/kg) completely prevented changes in 5-HT and 5-hydroxyindoleacetic acid seen following traumatization in untreated animals. These results provide evidence that decreased LCGU in lesioned brain is due to an activation of the serotonergic system. The data are thus in agreement with a postulated inhibitory role of serotonin in the cerebral cortex, and its involvement in functional alterations associated with injury.