The resistance of malignant tumors to chemotherapy is often associated with overexpression of the multidrug resistance gene MDR. Its gene product, P-glycoprotein, acts as a drug efflux pump for chemotherapeutic agents. The authors studied MDR expression in 28 adenocarcinomas arising in Barrett's esophagus (EAs) using a monoclonal antibody directed against this gene product. The results were compared with MDR expression in 27 gastric adenocarcinomas (GAs). P-glycoprotein was detected in both tumor and normal mucosa in 7 of 27 GAs and in 6 of 10 EAs that were resected without prior chemotherapy. Chemotherapy was given before surgical resection in 18 of the EAs studied. Five patients had a partial response to chemotherapy, and one had a complete eradication of his carcinoma; all of these tumors were negative for P-glycoprotein. Of 12 patients without chemotherapy response, 6 had tumors that expressed P-glycoprotein. The authors conclude that P-glycoprotein is present in EAs and GAs before exposure to chemotherapy. The presence of P-glycoprotein in tumors usually correlates with its presence in the adjacent mucosa. Its presence in tumor cells may be an indicator of lack of sensitivity to chemotherapy.