Since nitric oxide (NO) contributes to both circulatory disorders and host defense, we analyzed the NO production in (poly)trauma patients (pts) in a prospective (pre)clinical study starting as early as at the scene of accident. Upon approval of the local IRB/EC, 85 multiple injured pts were enrolled. Subsets were performed according to trauma severity (ISS) and injury pattern, and between survivors versus nonsurvivors. The first blood sample was collected at the scene of accident, then in hourly to daily intervals. NO production was assessed by measuring nitrate+nitrite plasma levels. To estimate dilution effects, all values were calculated according to the actual plasma protein content. The extent of trauma was appraised by C-reactive protein (CRP) levels. Immediately after trauma, N02- + N03- plasma levels were always elevated. This was most pronounced in thoracic injury, irrespective of whether it was combined with multiple trauma. Nitrate+nitrite levels returned to normal within 24 h. CRP generation increased during 12 h following trauma and was most marked in severest trauma (ISS >50). For the first time, we show very early data following major trauma that demonstrate that NO overproduction starts immediately after trauma. However, systemic N02-+ N03- levels actually reflect the severity of injury only during the first 2 h. Thereafter, NO generation is rather related to the individual trauma pattern, e.g., chest trauma. Nonetheless, the role of NO after severe trauma and especially in thoracic injury remains unclear and should further be elucidated in a specific study.