Previous studies have shown epidermal growth factor (EGF) to be involved in oral wound healing as well as gastric cytoprotection. EGF functions with hormone-like properties to stimulate epithelial cells by binding to the EGF receptor which ultimately leads to proliferation via signal transduction mechanisms. Salivary glands are a major source of EGF. The purpose of this study was to determine if intra-oral wounding by periodontal surgery stimulated increased salivary EGF levels. Salivary EGF levels were determined for 12 systemically healthy individuals (ages 27 to 70 years old) presurgically and postsurgically at 6, 12, 18, 24, 30, 36, and 42 hours and 2 and 6 weeks. Three ml of unstimulated whole saliva was obtained at each time point to allow immunoassay quantitation. Age and gender matched unoperated patients served as controls. Salivary samples were incubated with monoclonal and polyclonal EGF antibodies in these “sandwich” enzyme immunoassays. Quantitation was obtained by spectrometric analysis at OD 450 nm after addition of 200 μl of colorimetric substrate. Mean EGF levels ranged from 2441 pg/ml presurgically to 3349 pg/ml at 18 hours postsurgically and 1207 pg/ml at 6 weeks postsurgically. Repeated measures analysis of variance indicated statistically significant differences in 18 hours postsurgical salivary EGF levels when compared to controls and to postsurgical levels from 36 hours forward (P < 0.01). A second smaller rise in EGF was detected at 30 hours. These results suggest a transient increase in salivary EGF levels in response to intra-oral wounding. J Periodontol 1998;69:479–484.