Eosinophilic esophagitis (EE) and gastroesophageal reflux disease (GERD) have similar clinical presentations. The immunoregulatory mechanisms involved in both diseases are not clearly defined. We studied cellular inflammation in pediatric patients with EE and GERD compared to normal controls (NC). Pathology records were reviewed of 10 EE, 8 GERD, and 10 NC children who were seen at Texas Children's Hospital in the past 3 yr. FOXP3, CD4, CD8, CD25, eotaxin-3, and IL-5 immunohistochemical stains were performed on formalin-fixed, paraffin-embedded esophageal tissue sections and assessed by a blinded observer. The numbers of FOXP3(+), CD25(+), and CD8(+) cells were significantly increased in both EE and GERD compared with NC. No significant differences in the numbers of FOXP3(+), CD4(+), CD8(+), and CD25(+) cells were detected between the patients with EE and GERD. Eotaxin-3(+) was found in mature epithelial cells and IL-5 was detected in esophageal intravascular space in all 3 groups. Eosinophil degranulation and microabscesses were significantly increased in EE compared to GERD. IL-5 was detected in vessels of the affected esophageal area and eotaxin-3 is produced locally by mature epithelial cells. Increased numbers of esophageal FOXP3(+) regulatory T cells, and CD8(+) T cells in both EE and GERD suggest that a negative feedback mechanism may regulate the inflammatory response.