CD14 is a pattern recognition receptor on the membranes of monocytes and macrophages for several microbial products, of which lipopolysaccharide (LPS) is the best known. A shed form of CD14 is present in serum. As the CD14 gene promoter polymorphism -159C/T and some bacterial infections may affect the sCD14 levels, we compared the impact of both the CD14 promoter polymorphism and Helicobacter pylori infection on serum sCD14 levels in 201 dyspeptic patients (group 1) who had undergone gastroscopy, and 127 staff members (group 2) with no endoscopy. sCD14 was measured from the sera by a commercial enzyme immunoassay (EIA), and CD14 genotyping was carried out with PCR. Helicobacter pylori infection was detected by serology and/or culture or PCR. sCD14 levels were elevated in the subjects carrying the T allele (CT or TT genotype) in both groups when compared with subjects with the CC genotype. Overall, H. pylori-positive subjects tended to have higher sCD14 levels compared with H. pylori-negative subjects. In group 1 consisting of dyspeptic patients, those with gastric ulcer, gastric erosion or duodenal ulcer had significantly elevated levels of sCD14 compared with the patients with normal endoscopic findings or macroscopic gastritis. The recent use of NSAIDs was also associated with enhanced sCD14. Thus, we were able to show several factors, one genetic and the other environmental (H. pylori infection and mucosal lesion), to have an impact on sCD14.