The role of salivary epidermal growth factor (EGF) in the maintenance of ileal mucosal integrity was studied by evaluating the effects of sialoadenectomy on luminal EGF levels, ileal tissue resistance (Rt), and unidirectional flux of [51Cr]EDTA. Mice in groups 1 (SLX) and 2 (SLX + EGF) were subjected to sialoadenectomy, while mice in groups 3 (Sham) and 4 (Sham + EGF) underwent a sham procedure. All animals received normal diet and water, except that EGF (100 ng/ml) was added to water for SLX + EGF and Sham + EGF mice. At seven days after surgery, luminal EGF levels in gastrointestinal segments and ileal Rt were significantly reduced by sialoadenectomy, which was prevented by EGF supplementation. Unidirectional flux of [51Cr]EDTA was 6- to 22-fold greater in the ileum of sialoadenectomized mice, which was prevented by EGF administration. Results suggest that salivary EGF may be the major source of intestinal EGF, and it may play a role in maintenance of ileal mucosal integrity.