Cytokines are early responders in the cascade of host mediators after injury. The cytokine response in neonates following surgery and its prognostic significance were studied prospectively. Twenty-one patients (oesophageal atresia [5], congenital diaphragmatic hernia [4], exomphalos [4], patent vitellointestinal duct [1], anorectal anomaly [2], choledochal cyst [1], renal cyst [1], ovarian cyst [1], myelomeningocoele [1], and pyloric stenosis [1]) operated on at a median age of 3 days (range, 1 to 24 days) and 12 age-matched controls were included in the study. Plasma samples were obtained once in the controls, and serially preoperatively and at 1, 3, 6, 12, 24, 36, and 48 hours postoperatively in the patients. The levels of the cytokines, interleukin-6 (IL-6), and interleukin-8 (IL-8) were measured using the enzyme-linked immunosorbent assay (ELISA) technique. The median plasma levels of IL-6 and IL-8 in normal controls were 2.4 pg/mL and 92.0 pg/mL, respectively. Of the 21 patients, four had postoperative complications (pulmonary consolidation [2], septicaemia [1], and oesophageal leak [1]) between days 4 and 6. All 17 uncomplicated cases had an increase in IL-6 and IL-8 in the early postoperative period, with the peak occurring within 12 hours after surgery. The mean (+/- SEM) peak levels of IL-6 and IL-8 in uncomplicated cases were of 92.6 +/- 15.8 pg/mL and 230.3 +/- 45.3 pg/mL, respectively. In the four complicated cases, there was a disproportionately higher increase in both IL-6 (peaks, 305.0, 125.0, 240.0, and 220.0 pg/mL) and IL-8 (peaks, 1500.0, 340.0, 245.0, 355.0 and pg/mL), which preceded the clinical onset of complications. The early postoperative increases in plasma IL-6 and IL-8 probably represent the stress response of neonates to surgery. Furthermore, the association of an exaggerated increase in postoperative levels of plasma IL-6 and IL-8 and postoperative complications may have prognostic significance.