Surgical stress induces systemic endocrine-metabolic responses that influence the function of endothelial cells (EC) to cause various systemic reactions. Intercellular adhesion molecule (ICAM)-1 is an adhesion molecule that plays an important role in inflammation, and increased expression of ICAM-1 on EC is a reflection of EC activation. In this study, we investigated the ICAM-1 response to surgical stress in neonates undergoing major surgery. Fifteen neonates (mean age at surgery: 3.5 +/- 1.2 days) were divided into two groups according to indications for surgery: Group I: Congenital diaphragmatic hernia without persistent pulmonary hypertension (n = 5); Group II: Gastrointestinal surgery [n = 10: duodenal atresia (n = 3), intestinal atresia (n = 6), and esophageal atresia (n = 1)]. Serum samples were obtained preoperatively, immediately after completion of surgery (time zero), and 24, 48, 72, 96, and 120 h after surgery to measure ICAM-1 levels using an enzyme-linked immunosorbent assay, C-reactive protein (CRP), and white blood cell count (WBC). Postoperative recovery was uneventful in all cases. ICAM-1 levels in both groups increased significantly within 24 h of surgery (Group I: P = 0.0038, Group II: P = 0.0320). In Group I, ICAM-1 peaked 72 h postoperatively while in Group II it continued to rise until 96 h postoperatively. The difference between peak levels reached was not significant. CRP was first detected 24 h postoperatively in both groups and continued to increase until 48 h postoperatively. Again, the difference between peak levels reached was not significant. No significant changes in WBC were observed in either group. We found that ICAM-1 increases in response to surgical stress in neonates, although there was no significant difference in levels. However, surgical stress as represented by serum ICAM-1 would appear to last longer with intestinal surgery than with non-intestinal surgery. Further research is required to establish the usefulness of ICAM-1 as an easily detectable substance associated with endothelial damage that reflects the host's response to major surgical stress.