The role of duodenogastric reflux (DGR) in producing esophageal mucosal injury across the spectrum of GERD is still controversial. Our objective was to assess the role of DGR in the genesis and evolution of erosive esophagitis. Forty patients are presented who meet the criteria for the diagnosis of erosive esophagitis. Symptom scoring, endoscopy and mucosal biopsy with patohistologic classification of erosive esophagitis and a quantification of DGR, using scintigraphic imaging after intravenous injection of 99mTc-labeled HIDA, was performed. DGR was demonstrated in half of the patients. Both groups of patients (with and without DGR) were treated with life style changes, cisapride and nizatidine for a period of six weeks. After this period, symptom scoring, endoscopy and biopsy were performed again in both groups. There has been a significant decrease in the level of symptom scoring and endoscopic inflammation after the therapy, but without statistically significant difference between these two groups. Patohistologic finding after the medical treatment showed a marked difference between the two groups concerning the presence of DGR, indicating that the level of inflammation is statistically significantly higher in the group with DGR. This study showed that even if symptom scoring and endoscopy revealed improvement after the therapy in both groups of patients, patohistologic mucosal damage in patients with erosive esophagitis is greatly dependent of the presence of DGR. We conclude that alkaline component of GERD should be considered in the evaluation of patients with erosive esophagitis so that appropriate surgical therapy can be instituted.