The stomach is the main source of circulating ghrelin. Plasma concentrations of this hormone in patients with various upper gastrointestinal diseases remain undetermined. Thus we measured plasma ghrelin levels by radioimmunoassay in 225 subjects, including 134 Helicobacter pylori-infected and 91 uninfected subjects. They included 67 patients with chronic gastritis (CG), 26 with benign gastric polyp (BGP), 24 with gastric ulcer (GU), 24 with reflux esophagitis (RE), 18 with duodenal ulcer (DU), 28 with acute gastritis (AG), 23 with gastric cancer (GC), and 39 who had normal mucosa on upper endoscopy (N). Plasma pepsinogen I and II levels were also measured. The extent of gastritis was assessed endoscopically. Ghrelin levels differed significantly among the different disease groups. Plasma ghrelin concentrations were lowest in the CG group, followed by the GU group, and highest in the AG patients. There was a significant difference in the levels between differentiated and undifferentiated GC. Ghrelin concentrations in BGP, RE, and DU patients were comparable to those in the N group. Ghrelin circulating levels were lower in H. pylori-positive than -negative individuals, but the significant differences among disease groups were still observed in H. pylori-infected and uninfected populations. Ghrelin concentrations correlated positively with plasma pepsinogen I levels and I/II ratios and inversely with the extent of H. pylori-related gastritis. Plasma ghrelin levels varied widely in diverse conditions of the upper digestive tract, reflecting the inflammatory and atrophic events of the background gastric mucosa. Further investigation is warranted to unravel the mechanisms of the high circulating ghrelin levels in certain upper gastrointestinal diseases.