Sepsis is a major complication of total parenteral nutrition (TPN) in children. Gut mucosal atrophy (GMA) and bacterial translocation (BT) occur in patients receiving TPN, and the translocated enteric organisms may cause central venous catheter (CVC) infection. Epidermal growth factor (EGF) has a trophic effect on the gut mucosa and may reduce BT, thereby reducing catheter infection. Using a rat TPN model, the relationship between GMA, BT, and catheter sepsis was examined and the effect on these of intravenous EGF was studied. There were four experimental groups. Group 1 had no CVC, Groups 2, 3, and 4 had a continuous central venous infusion as follows: group 2, saline; group 3, TPN; group 4, TPN with EGF. Groups 1 and 2 had free access to chow, groups 3 and 4 had no enteral feeds. After killing at 1 week, blood, tissue, and catheter specimens were cultured and mucosal morphology analysed. BT was defined as the presence of the same organism in cultures from the gut lumen and mesenteric lymph nodes (MLN). TPN only (group 3) resulted in GMA and BT, and 5 of 12 animals with BT had the same gut bacteria in blood and/or catheter cultures. The addition of EGF to the TPN significantly reduced GMA, BT to the MLN, and blood and/or catheter infections (P = <0.05). In animals carrying enterococci, there was a significant reduction in translocation of enterococci (group 3: 8/14; group 4: 0/11; P<0.05) and catheter infection by enterococci was prevented (group 3: 3/14; group 4: 0/11). EGF thus reduced GMA, BT, and blood and/or catheter infection when given IV to rats receiving TPN. Enterococcal translocation and subsequent blood and/or catheter infection was completely prevented, suggesting a selective effect of EGF.