Background:The histological diagnosis of GERD is not based on a single feature in esophageal biopsies. However, the presence of eosinophils is considered a sensitive marker for GERD. A morphological finding that can also be seen in GERD is spongiosis, which is the presence of edema between squamous cells. However, the relationship between spongiosis, eosinophils and other histological features attributed to GERD has not been analyzed in detail. Methods: Histological sections of 57 well-oriented esophageal biopsies were examined microscopically for the presence of eosinophils. The latter were quantified per 10 high power fields (hpf). Spongiosis was graded as absent, mild, moderate and severe (0-3). Parallel sections were stained for PAS and evaluated for the thickness of the basal cell layer component and measured by using an ocular micrometer. The number of layers of basal cells were also counted. Other findings that were quantified included intraepithelial lymphocytes, congestion of the tips of the papillae, neutrophilic infiltrates, hyperkeratosis, hypergranulosis and ulceration. For statistical analysis, the Spearman rank order test was used. Results: 35 biopsies lacked eosinophils and 22 had eosinophils that ranged from 1 to 60 per 10 hpf. Spongiosis was seen in 96% of the cases with eosinophils and in only 74% of the cases without eosinophils. There was a positive correlation (p=0.003) between the presence of eosinophils and spongiosis with 0.09, 0.95, 2.14 and 14 eosinophils per 10 hpf in grades 1, 2, and 3 of spongiosis, respectively. The average thickness of the basal cell layer for the cases with esinophils was 0.26 mm; whereas, for those without eosinophils it was 0.19 mm (p=0.03). Basal cells occupied 27.7% of the full thickness of the squamous mucosa in cases infiltrated by eosinophils and 23% in the cases without eosinophils. There was no correlation with intraepithelial lymphocytes, neutrophilic infiltrates, congestion, ulceration, hyperkaratosis or hypergranulosis. Conclusion:The presence of spongiosis in esophageal biopsies is associated with eosinophilic infiltrates and thus may help in the histologic diagnosis of GERD. Additional studies are needed to correlate with the clinical impression of GERD.