Objective: To examine the relationship of circulating proinflammatory and anti inflammatory cytokine concentrations to nitric oxide and organ failure in pediatric sepsis, Design: Prospective study, Setting: Pediatric intensive care unit (ICU), Children's Hospital of Pittsburgh, University of Pittsburgh. Patients: Nineteen patients with a diagnosis of sepsis admitted to the pediatric ICU, Twelve uninfected critically ill patients served as controls, Interventions: None, Measurements and Main Results: Plasma interleukin (IL)-10, IL-6, and nitrite/nitrate concentrations were measured and compared with an index of organ failure daily for 3 days after presentation with the sepsis syndrome, Children with increased plasma IL-6 concentrations (n = 6) had increased plasma nitrite/nitrate concentrations (p < .01 on each day), increased organ failure scores (p < .05 on days 2 and 3), and the highest plasma IL-10 concentrations (p < .05 on days 1 and 3, p = .054 on day 2) when compared with children with sepsis and undetectable IL-6 concentrations. Children with sepsis and detectable IL-6 concentrations, and children with undetectable IL-6 concentrations, both had increased nitrite/nitrate concentrations (p < .005 on days 1 through 3) and increased IL-10 concentrations (p > .05 on days 1 and 2) compared with controls, Children with in creased IL 6 concentrations had higher organ failure on each day (p < .01), and children with undetectable IL-6 concentrations had higher organ failure on days 1 and 2 only (p < .005) when compared with controls, Organ failure improved over time in the children with undetectable IL-6 concentrations (p < .005). Conclusions: Increased plasma nitrite/nitrates and increased organ failure scores occurred in the children with sepsis who had an exaggerated proinflammatory state, despite a pronounced antiinflammatory response, When the anti-inflammatory response predominated, and the proinflammatory state was dampened, organ failure status improved.