The mediators responsible for maintenance of the hyperdynamic state and the low systemic vascular resistance (SVR) observed in sepsis have not been elucidated. Nitric oxide (· N = O) is a mediator with numerous functions, including regulation of vascular tone and a role in macrophage-mediated cytostasis and microbiostasis. Thirty-nine critically ill trauma and septic patients were studied to determine the relationship between · N = O production and the hyperdynamic state. High plasma levels of NO2-/NO3- (the stable end products of · N = O) were observed in septic patients (p < 0.02). Low SVR and high endotoxin levels were associated with high NO2-/NO3- values (p = 0.029, p = 0.002). Changes in · N = O levels may mediate the vasodilation seen in sepsis. Low NO2-/NO3- levels were observed in trauma patients (p < 0.001) and remained low even in the presence of sepsis (p = 0.001).