Background: Cox-2 is an inducible enzyme that is known to be involved in both inflammation and gastrointestinal carcinogenesis. Clinical studies on Barrett’s esophagus (BE) have shown that inflammation is greatest at the proximal end of the segment, while cancers occur more commonly in the distal end. To determine if upregulation of Cox-2 in BE is secondary to inflammation or tumorigenesis, we compared gene expression of Cox-2 and IL-8, a more specific marker of inflammation, throughout the length of long segment BE. Methods: Endoscopic biopsies were taken at 2 cm increments in 4 quadrants from 15 patients with long segment, non-dysplastic BE. The paraffin embedded tissue blocks were sectioned and microdissected. RNA was isolated, reverse transcribed to cDNA, and gene expression was measured using quantitative real-time PCR relative to the reference gene β-actin. Patients were off acid suppression therapy and none had previous foregut surgery. Results: Median BE length was 8 cm (range 4-17). Both Cox-2 and IL-8 gene expression were highest at the top of the BE segment, with significantly lower expression at the bottom (Figure). Biopsies from the distal 3 cm of the Barrett’s segment showed intestinal metaplasia in 37 and cardiac mucosa in 7, and Cox-2 and IL-8 expression were similar in both types of mucosa (p=0.19). Conclusion: Cox-2 expression parallels IL-8 expression in long segment BE. An expression gradient exists for both genes along the Barrett’s segment, with highest expression at the top. This suggests that upregulation of Cox-2 is initiated by inflammation and occurs prior to neoplastic changes.