Cytokines play a major role in renal scar formation following febrile urinary tract infection (UTI). We investigated the role of dexamethasone combined with antibiotics in diminishing urinary interleukin-6 (UIL-6) and UIL-8 concentrations during the acute phase of pyelonephritis compared with standard antibiotic therapy. UIL-6 and UIL-8 concentrations were determined by enzyme immunoassay in 34 children with pyelonephritis who were treated with ceftriaxone plus dexamethasone (case group) and in 20 patients with the same diagnosis treated with ceftriaxone alone (control group). Urine samples were obtained at the time of presentation prior to drug administration and at follow-up 72 h after initiation of medication. Creatinine concentrations were also determined, and cytokine/creatinine ratios were calculated to standardize samples. Differences between cytokine/creatinine ratios in initial and follow-up urine samples were significant in the case group (P < 0.001) but not for controls. In addition, combined antibiotic and dexamethasone significantly decreased UIL-6 and UIL-8 concentrations compared with antibiotic alone (P < 0.05). We conclude that dexamethasone combined with antibiotics significantly decreases UIL-6 and UIL-8 levels in patients with acute pyelonephritis. This suggests that the clinical use of corticosteroids may prevent scar formation following febrile UTI.