Because of the possible involvement of cytokines in gram-negative septicemia, we investigated serum levels of tumor necrosis factor alpha, interleukin-1 beta, alpha interferon, and gamma interferon in children with gram-negative sepsis and purpura fulminans. We studied 55 patients (ages, 1 month to 19 years) with a clinical diagnosis of sepsis and purpuric lesions who were in shock or had three or more other biologic risk factors. The mortality rate was correlated with the number of risk factors present on admission to the hospital (P = 0.03). Tumor necrosis factor alpha was elevated in 91 percent of the 35 patients tested, interleukin-1 in 21 percent of the 33 patients tested, and gamma interferon in 19 percent of the 32 tested. Alpha interferon levels were within normal limits in the 32 patients tested. Serum levels of tumor necrosis factor alpha were positively correlated with the number of risk factors (P less than 0.05) and negatively correlated with blood fibrinogen levels (P = 0.01). Tumor necrosis factor alpha, interleukin-1, and gamma interferon were significantly higher in patients who died than in the survivors. Alpha interferon levels were similar in the two groups. Serum concentrations of both interleukin-1 and gamma interferon were correlated with concentrations of tumor necrosis factor alpha. These data provide evidence that serum levels of tumor necrosis factor alpha, interleukin-1, and gamma interferon correlate with the severity of meningococcemia in children. The findings may have implications for new therapeutic approaches.