Eosinophils participate in the pathogenesis of inflammatory diseases of the respiratory tract and the gut. We investigated the constitutive presence of eosinophils and mononuclear cells in the macroscopically normal duodenal mucosa of patients with asthma and allergic rhinitis. Macroscopically normal duodenal specimens were obtained at routine endoscopy for upper gastrointestinal symptoms from 16 patients with asthma and 13 patients with allergic rhinitis. Twelve nonatopic patients with irritable bowel syndrome were studied as controls. Specimens were analyzed by immunohistochemistry using a panel of antibodies to human eosinophil cationic protein clone EG1 (EG1) and clone EG2 (EG2), anti-human interleukin (anti-hIL)-5, anti-hIL-4, anti-CD4, and anti-CD68. Significantly increased numbers of eosinophils stained with EG1 and EG2 were found in the duodenum of patients with asthma and allergic rhinitis compared with controls. IL-5+ cells and IL-4+ cells were detected in significantly increased numbers in the duodenal mucosa of patients with asthma and rhinitis compared with controls. Mononuclear cells expressing CD4 (helper T cells) and CD68 (macrophages) also were significantly increased in the duodenal mucosa of asthma and rhinitis compared with controls. Accumulation of eosinophils in conjunction with IL-4+ cells and IL-5+ cells in the noninflamed duodenal mucosa may reflect a predominant T helper cell subset 2 systemic immune response in patients with asthma and allergic rhinitis. The absence of intestinal inflammation despite the marked presence of cells implicated in the allergic inflammation suggests that local mechanisms might determine the state of nonresponsiveness in the gut mucosa of patients with asthma and allergic rhinitis.