Despite improvements in intensive care and the use of broad spectrum antimicrobial agents, bacterial sepsis remains an important cause of morbidity and mortality in infants. Cytokines are endogenous mediators elaborated during the pathogenesis of infection. We reported elevated levels of interleukin-6 and tumor necrosis factor in critically ill infants with sepsis and necrotizing enterocolitis. Interleukin-8(IL-8), a cytokine which attracts and activates neutrophils, may also be implicated in the inflammatory response. We hypothesized that plasma levels of IL-8 are elevated in infants with bacterial sepsis. We prospectively measured plasma IL-8 levels at presentation in infants <6 months of age who were evaluated for sepsis. Twenty infants had culture proven bacterial sepsis (GA 32.7±1.3 wk, M±SEM, postnatal age (PNA) 49±10 d); 20 control infants had signs of infection(sepsis syndrome) but negative cultures (GA 35.1±1.3 wk, PNA 24±8 d). Cytokine levels were determined by ELISA (T Cell Diagnostics, Woburn, MA). IL-8 levels were significantly elevated in infants with bacterial sepsis (306±113 pg/ml) versus sepsis syndrome controls (38±14 pg/ml, p<0.025). Furthermore, IL-8 levels were nearly tenfold greater in infants with gram negative (554±200 pg/ml, n=10) versus gram positive sepsis (58±21 pg/ml, n=10, p<0.025). Elaboration of IL-8 was independent of BW, GA, and PNA. Thus, IL-8 levels are elevated in infants with bacterial sepsis versus sepsis syndrome controls; these levels are highest during gram negative septicemia. In the future, cytokine determinations may identify infants who would benefit from immunotherapeutic strategies. (Funded by NIH RR-00240).