The synthesis of prostaglandin E2 (PGE2) requires cyclooxygenase (COX) and prostaglandin E synthase (PGES). There are two forms of PGES: cytosolic PGES (cPGES) and microsomal PGES (mPGES)-1. In this study, we investigated the effects of gastroesophageal reflux (GER) contents on PGES and COX-2 in esophageal cells. We incubated a human normal esophageal cell line, two esophageal squamous cell carcinoma (SCC) cell lines, and two esophageal adenocarcinoma (ADC) cell lines with GER contents. The production of PGE2 by these cells was assayed with an enzyme immunoassay kit. The protein expression of COX-2, cPGES, and mPGES-1 was confirmed by immunoblot analysis. The following results were obtained: GER contents induced the expression of COX-2 in all five cell lines. In normal esophageal cells, cPGES, but not mPGES-1, was detected in the cytosolic fraction. GER contents induced the expression of cPGES in the microsomal fraction. In SCC cells, cPGES was expressed in the cytosolic fraction, and mPGES-1 was expressed in the microsomal fraction. GER contents induced the expression of mPGES-1 in the microsomal fraction. In ADC cells, cPGES was expressed in both the cytosolic and microsomal fractions. GER contents induced the expression of both cPGES and mPGES-1 in the microsomal fraction. In conclusion, our results suggest that GER contents induce PGE2 production in esophageal cells. However, there are different isoforms of PGES in normal cells, SCC cells, and ADC cells.