Nitric oxide (NO) has important regulatory functions within the central nervous system. NO is oxidized in vivo to nitrate and nitrite (NO(x)). Measurement of these products gives an index of NO production. The purpose of this study was to examine the relation between the brain extracellular concentration of NO metabolites and cerebral blood flow (CBF) after severe traumatic brain injury. Using a chemiluminescence method, NO(x) concentrations were measured in 6,701 microdialysate samples obtained from 60 patients during the first 5 d after severe head injury. Regional and global values of CBF obtained by xenon-enhanced computed tomography were used for analyses. Dialysate NO(x) values were the highest within the first 24 h after brain trauma and gradually decreased over the 5 postinjury d (time effect, P < 0.001). Mean dialysate concentration of NO(x) was 15.5 +/- 17.6 micromol/L (minimum 0.3, maximum 461 micromol/L) and 65% of samples were between 5 and 20 micromol/L. There was a significant relation between regional CBF and dialysate NO(x) levels (r2 = 0.316, P < 0.001). Dialysate NO(x) levels (9.5 +/- 2.2 micromol/L) in patients with critical reduction of regional CBF (<18 mL. 100 g-1. min-1) were significantly lower than in patients with normal CBF (18.6 +/- 8.1 micromol/L; P < 0.001). This relation between the dialysate concentration of NO(x) and regional CBF suggests some role for NO in the abnormalities of CBF that occur after traumatic brain injury.