We previously demonstrated that in esophageal mucosal biopsies, intraepithelial cells with irregular nuclear contours (CINC) as well as mononuclear cells with round nuclei are T-lymphocytes and we suggested that they may be an independent marker of esophagitis. To investigate this hypothesis, we evaluated Hematoxylin and eosin-stained biopsy specimens from 201 consecutive patients (115 female, 86 male; mean age: 52 years) that showed either no accepted features of esophagitis (n = 122) or changes typical of esophageal reflux (n = 79). The number of intraepithelial CINC and mononuclear cells in the most densely populated high power field were counted. Twenty-two of these biopsies were also stained with UCHL-1 (T-lymphocyte marker) and L-26 (B-lymphocyte marker). All medical records were reviewed to determine clinical and endoscopic findings of esophagitis, which were then compared with the histologic results for correlations. The immunohistochemical results confirmed that the majority (> 95%) of CINC and mononuclear cells were T-lymphocytes, and the sum of CINC and mononuclear cells represents best the number of T-lymphocytes. The number of T-lymphocytes was significantly correlated with that of eosinophils (R = 0.24, P = 0.0008) but not with neutrophils (R = 0.069, P = 0.33). They were greater in number, although not significantly so, in the specimens with histologic evidence of esophagitis than those without (12.7 +/- 8.9 versus 11.3 +/- 7.7, P = 0.23).(ABSTRACT TRUNCATED AT 250 WORDS)