Esophageal carcinoma includes squamous cell carcinoma and Barrett's adenocarcinoma. The latter usually develops from a premalignant lesion named Barrett's esophagus. MUC genes are known to be specifically expressed in the normal, premalignant and malignant epithelia of various tissues. The aim of this study was to establish the pattern of MUC gene expression in the esophageal mucosa under normal conditions, and under pathological conditions such as squamous cell carcinoma, Barrett's esophagus and adenocarcinoma. Samples of esophageal control mucosa, metaplastic and malignant tissues were obtained from 40 patients undergoing esophagectomy for squamous cell carcinoma (n ؍ 17), or Barrett's esophagus with adenocarcinoma (n ؍ 23). In situ hybridization and northern blot were used with probes specific for the MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6 and MUC7 genes to assess their expression in these samples. Submucosal glands of control esophageal mucosa expressed MUC5B, whereas MUC1 and MUC4 were found in both control epithelium and squamous cell carcinoma. MUC4 expression correlated with squamous cell differentiation. Barrett's adenocarcinoma exhibited various patterns of MUC gene expression, the strongest being in the well-differentiated mucinous adenocarcinomas. Barrett's metaplasia was also associated with a specific MUC gene expression pattern, since the gastric apomucin mRNAs, MUC5AC and MUC6, were expressed in gastric metaplasia, and the intestinal apomucin mRNAs, MUC3, MUC4 and mostly MUC2, in intestinal metaplasia. Residual expression of gastric apomucin mRNAs was found in intestinal metaplasia. From these results, we conclude that MUC genes can be considered reliable phenotypic markers of the esophageal cell differentiation, thus providing new insight into the development of Barrett's esophagus.