Our aim was to determine whether p53 and Rab11a immunoreactivity enhance diagnostic assessment of esophageal dysplasia. Histologic sections from 68 cases of Barrett esophagus obtained as part of a 12-institution study were stained with antibodies to p53 and Rab11a, randomized, and coded. The mucosal surface layer and deeper glands were scored blindly on a semiquantitative scale. The correlations between p53 and Rab11a scoring with the consensus diagnosis of dysplasia were analyzed. The histologic scale was as follows: no dysplasia, indefinite, low-grade dysplasia, high-grade dysplasia, intramucosal carcinoma, and invasive carcinoma. Rab11a staining was most prominent in epithelia negative for dysplasia but with regenerative features. There was an inverse relationship between Rab11a staining and findings of surface dysplasia (P < .02, chi(2)). However, statistical significance largely reflected loss of Rab11a immunoreactivity in intramucosal and invasive carcinoma, which was not a diagnostic dilemma. There was a strong positive correlation of p53 immunoreactivity with an increasing degree of epithelial dysplasia and carcinoma (P < .03, chi(2)). Rab11a immunoreactivity did not enhance the diagnostic assessment of dysplasia in Barrett esophagus. The previously reported positive correlation of p53 immunoreactivity with the presence of dysplasia in Barrett esophagus was confirmed.