It has been demonstrated recently that salivary epidermal growth factor (sEGF) output in healthy individuals is strongly and significantly influenced by esophageal intraluminal mechanical and chemical stimuli. Therefore, we have studied the impact of intraesophageal mechanical and chemical stressors on the rate of secretion of sEGF in 14 patients with reflux esophagitis (RE), and compared these results with corresponding parameters measured in 14 sex- and age-matched controls. EGF was assessed in saliva collected during basal conditions, chewing of parafilm, placement of esophageal tubing, inflation of intraesophageal balloons, and perfusion with NaCl, HCl, and HCl/pepsin solutions. The concentration of sEGF was measured with an RIA kit from Amersham (Arlington Heights, IL). The concentrations of sEGF were (mean +/- SEM) 2.50 +/- 0.32 ng/ml and 2.00 +/- 0.37 ng/ml in basal saliva and during stimulation by chewing the parafilm, respectively. Basal sEGF value appeared to be significantly higher than in controls (2.50 +/- 0.32 vs. 1.90 +/- 0.22 ng/ml, p < 0.05, in one-tailed t test). Placement of intraesophageal tubing resulted in a significant decline of sEGF concentration, compared with parafilm-stimulated conditions (1.25 +/- 0.12 vs. 2.00 +/- 0.37 ng/ml, p < 0.0001) and corresponding tubing-stimulated sEGF value in controls (1.25 +/- 0.12 vs. 1.52 +/- 0.16 ng/ml, p < 0.05). sEGF concentrations after inflation of intraesophageal balloons and subsequent perfusion with initial saline, HCl, HCl/pepsin, and ending saline were also highly significantly lower (1.05 +/- 0.18 ng/ml, p < 0.001; 1.10 +/- 0.20 ng/ml, p < 0.001; 1.10 +/- 0.18 ng/ml, p < 0.001; 1.10 +/- 0.19 ng/ml, p < 0.001; and 1.05 +/- 0.18 ng/ml, p < 0.001, respectively) than sEGF concentration recorded during stimulation with parafilm. Concentrations of sEGF during esophageal perfusion with HCl, HCl/pepsin, and ending saline were also significantly lower than corresponding values in controls (1.10 +/- 0.18 vs. 1.49 +/- 0.11 ng/ml, p < 0.05; 1.10 +/- 0.19 vs. 1.59 +/- 0.11 ng/ml, p < 0.05; and 1.05 +/- 0.18 vs. 1.65 +/- 0.13 ng/ml, p < 0.01, respectively). The rate of sEGF output, which was 1.30 +/- 0.24 ng/min during basal conditions, increased significantly during stimulation with parafilm (2.30 +/- 0.38 ng/min, p < 0.05). Both basal and parafilm-stimulated sEGF outputs were somewhat higher, although nonsignificantly, than corresponding values recorded in healthy individuals. Mechanical and chemical stimulation (initial NaCl, HCl, and ending NaCl) failed to evoke a significant increase in sEGF output over the value observed during parafilm stimulation in patients with RE, although such a significant increase was clearly demonstrated in healthy individuals. Therefore, sEGF output in patients with RE remained significantly lower than corresponding values recorded in controls during an entire mechanical stimulation (2.65 +/- 0.35 vs. 4.60 +/- 0.85 ng/min, p < 0.001, after placement of intraesophageal tubing and 2.80 +/- 0.54 vs. 5.15 +/- 0.70 ng/min, p < 0.001, after inflation of balloons). sEGF output in patients with RE remained also significantly lower than adequate control values during chemical stimulation (3.65 +/- 0.64 vs. 5.20 +/- 0.60 ng/min, p < 0.05, during perfusion with initial saline; 3.70 +/- 0.70 vs. 5.20 +/- 0.60 ng/min, p < 0.05, during perfusion with HCl; 3.70 +/- 0.52 vs. 5.55 +/- 0.72 ng/min, p < 0.01, during perfusion with HCl/pepsin, and 3.30 +/- 0.56 vs. 5.80 +/- 0.86 ng/min, p < 0.001, during ending saline). Impairment in sEGF secretion during mechanical and chemical intraesophageal stimulation, mimicking the natural scenario occurring during gastroesophageal reflux, may facilitate the development of esophageal mucosal pathology and delay the healing of already developed mucosal injury.