A subepitheal myofibroblastic (SMF) cell layer has been described in the colon, and referred to as pericryptal myofibroblastic cell layer. SMF cells have been shown to produce basement membrane proteins, including type IV collagen and laminin. The aim of this work was to determine the status of the SMF cell layer in Barrett's metaplasia (BM), with and without dysplasia, and compare that to the previously reported distribution of SMF in normal colon and colonic adenomas and carcinoma. Sections of formalin-fixed, paraffin-embedded biopsies from 6 colonic adenomas and 5 colonic adenocarcinomas, as well as 4 cases of BM without dysplasia, 4 with low grade dysplasia, 4 high grade dysplasia and 4 with invasive adenocarcinoma were immunohistochemically stained for alpha smooth muscle actin using the immunoperoxidase method. A continuous layer of SMF cells was present in all normal colonic tissue and adenomas but was absent in all colorectal adenocarcinomas. Surprisingly, none of the cases of BM with or without dysplasia or carcinoma showed an organized SMF cell layer. Unlike the colon, the SMF cell layer is absent in BM even without dysplasia. We hypothesize that lack of the SMF cell layer in BM may contribute to the quick progression to esophageal adenocarcinoma, which, unlike that in the colon, occurs before an exophytic lesion becomes evident.