OBJECTIVE: To determine eosinophil and mast cell populations in gastric and duodenal mucosal biopsies of adults with nonulcer dyspepsia (NUD) as compared to non-dyspeptic adults. STUDY DESIGN: A case control study. PLACE AND DURATION OF STUDY: Shahid Sadoughi University of Medical Sciences, Yazd, Iran, from January 2010 to June 2011. METHODOLOGY: A total of 52 (25 non-ulcer dyspeptic patients as case and 27 non-dyspeptic patients as control) patients underwent endoscopy. All patients had a minimum of 2 forceps biopsies obtained from stomach and duodenum. Routine histological evaluation was performed and additionally evaluated to determine eosinophil and mast cell counts. The statistical analysis was performed on SPSS version 17.0, using Mann-Whitney test with significance at p < 0.05. RESULTS: The mean age in the case and control groups was 31.72 ± 12.17 and 35.74 ± 12.42 years respectively. The median eosinophil density in gastric mucosa in case group was 5.0 (ranging from 1 to 20) and 4.0 in control group (ranging from 0 to 16; p = 0.140). The median eosinophil density in duodenal mucosa in case group was 16.0 (ranging from 2 to 24) and 13 in control group (ranging from 2 to 45; p = 0.147). The median mast cell density in gastric mucosa in case group was 4.0 (ranging from 0 to 33) and 4.0 in control group (ranging from 0 to 26; p = 0.827). The median mast cell density in duodenal mucosa in case group was 4.0 (ranging from 0 to 31) and 3.0 in control group (ranging from 1 to 23; p = 0.704). The frequency of Helicobacter pylori infection in both the groups was similar. CONCLUSION: Although there were not statistically significant differences in eosinophil and mast cell densities between case and control groups, there was a trend toward mild eosinophilia in gastric and duodenal mucosa. The specific role of eosinophils and mast cells in NUD is yet to be completely defined.