The diagnostic usefulness of intraepithelial cells with irregular nuclear contours (CINC) (squiggle cells) in esophageal biopsies was investigated in 76 children (range age: 6 months-12 years) with gastroesophageal reflux disease. A further 20 subjects (range age: 10 months-11 years) served as controls. Based on the microscopic changes of the esophagus, according to traditional histological criteria, four groups of patients were identified; esophagitis was severe in 27, moderate in 20, mild in 21, and 8 patients had no clear-cut evidence of microscopic esophagitis. Data are given as mean +/- SD. Intraepithelial CINC had an immunohistochemical profile consistent with T lymphocytes. Patients with severe esophagitis had a CINC density (number per high-power filed) (9.0 +/- 3.5) significantly higher than patients with mild esophagitis (7.0 +/- 3.0) and those without evidence of microscopic esophagitis (6.5 +/- 1.9) (P < 0.05), but not different from those with moderate esophagitis (8.0 +/- 3.6); in all patients groups the CINC density was higher than in controls (2.2 +/- 0.3) (P < 0.01). The percentage of reflux at 24-hr intraesophageal pH monitoring was higher in severe esophagitis patients (11.4 +/- 6.0) as compared to the other groups (moderate: 7.8 +/- 6.3; mild: 6.5 +/- 3.6; no microscopic esophagitis: 6.3 +/- 2.0; P < 0.05). There was no correlation between CINC density and the amount of intraesophageal acid exposure in all patients. Furthermore, 27 of our patients had a normal intraesophageal acid exposure at the prolonged pH test (24-hr % of reflux < or = 4.5): the CINC density was significantly higher in them than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)