Cytokines are thought to be important endogenous mediators of the host immune response to bacterial infection. We hypothesized that plasma levels of cytokines are elevated in children with sepsis and that the magnitude of elevation of these cytokines is correlated with severity of illness and mortality rate. We determined plasma levels of tumor necrosis factor, interleukin-6, and interleukin-1 in 21 children with sepsis. Plasma samples were collected at presentation and at 12, 24, and 48 hours thereafter. Cytokine levels were elevated in pediatric patients with bacterial sepsis during the first 48 hours after presentation; levels were undetectable in study control subjects. The tumor necrosis factor and interleukin-6 levels (p less than 0.001), as well as levels of interleukin-1 (p = 0.05), were significantly higher in nonsurvivors than in survivors and were independent of severity of illness (pediatric risk of mortality (PRISM) score) at presentation. Elevations of tumor necrosis factor and interleukin-6 were sustained for longer than 24 to 48 hours in nonsurvivors: II-1 concentrations were significantly increased only at time zero. Of 11 children with an interleukin-6 value greater than 2 ng/ml during the first 48 hours, 10 died; only one of 10 not reaching that level died (p less than 0.001). Cytokines were elevated as frequently with gram-positive as with gram-negative infections. We speculate that cytokine determinations may identify children who might benefit from immunotherapeutic interventions.