Objectives: This study was performed to determine serum concentrations of interleukin-6 (IL-6) during bacterial infections in the first week of life and to evaluate the usefulness of IL-6 as a diagnostic test for perinatal bacterial infections, alone and in combination with C-reactive protein (CRP). Study design: Blood was obtained from 241 newborn children on admission to the neonatal intensive care unit and at 3 to 4 days after admission. Both samples were analyzed for IL-6, CRP, and white blood cell count with differential. Results: Twenty-four newborns were classified as having an infection. Increased serum IL-6 levels were detected in infected compared with noninfected newborns on admission (p < 0.0001). Detection of IL-6 (≥20 pg/ml) alone yielded a sensitivity of 78%, a specificity of 71%, a positive predictive value of 40%, and a negative predictive value of 93%. A combined parameter of IL-6 (≥50 pg/ml) and CRP (≥10 mg/L) yielded a sensitivity of 96%, a specificity of 74%, a positive predictive value of 49%, and a negative predictive value of 99%. Conclusions: Used in combination with CRP, IL-6 seems to be a valuable parameter in the early diagnosis of neonatal infections. (J Pediatr 1998;132:295-9)