Current hypotheses concerning the histogenesis and regression of Barrett's oesophagus are based predominantly on animal models. Our study was formulated to assess, in human tissue, the morphological relationship between oesophageal gland ducts and both Barrett's oesophagus and their associated squamous islands. Serial sections were cut through a total of 46 blocks of archived oesophageal resection tissue containing oesophageal gland ducts underlying Barrett's epithelium. Serial sections were also taken through 15 squamous islands, taken from the same archived tissue, to assess their underlying histology: 21 of the ducts opened onto overlying Barrett's epithelium; in 17 there was a relatively sharp distinction between the two cell types, at the junction, whereas in four there was continuity and a gradual morphological change between the cells of the oesophageal gland ducts and the Barrett's epithelium. All 15 squamous islands sectioned were found to be continuous with an underlying gland duct. This study suggests an interrelationship between Barrett's epithelium and oesophageal gland ducts. More definitively we confirm that squamous islands are universally associated with oesophageal gland duct epithelium. These findings are of fundamental importance for the development of more targeted management strategies for Barrett's oesophagus. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.