Alterations in the tumor suppressor gene p53 may represent a useful prognostic marker of premalignant or malignant disease in Barrett's dysplasia or esophageal adenocarcinoma. Immunohistochemistry was used to establish the ability to detect nuclear accumulation of altered p53 protein in esophageal brushings as well as biopsies, and to examine for p53 alterations in a group of 18 patients with Barrett's esophagus enrolled in a surveillance and endoscopy program, p53 protein accumulation was easily detected in esophageal brushings, and the results correlated well with matched biopsies (9/11). In patients enrolled in surveillance endoscopy, 1 brushing of 22 was positive for p53 protein accumulation. In this patient, who received preoperative radiation and chemotherapy, the positive p53 result correlated with positive cytology for residual adenocarcinoma. All Barrett's esophagus brushings negative for p53 protein were benign by cytologic, morphologic criteria. The immunohistochemical detection of p53 alterations in esophageal brushing and biopsy specimens may provide useful information in patients undergoing surveillance for esophageal dysplasia and adenocarcinoma.