Impaired braking of inflammatory cell cysteinyl leukotriene production by prostaglandin (PG) E(2) has been implicated in the pathogenesis of aspirin exacerbated airways disease, but the mechanism is obscure. PGE(2) acts via G-protein-coupled receptors, E-prostanoid (EP)(1-4,) but there is little information on the expression of PGE(2) receptors in this condition. To address the hypothesis that expression of 1 or more EP receptors on nasal mucosal inflammatory cells is deficient in patients with aspirin-sensitive compared with nonaspirin-sensitive polypoid rhinosinusitis. By using specific antibodies, immunohistochemistry, and image analysis, we measured the expression of EP(1-4) in nasal biopsies from patients with aspirin-sensitive (n = 12) and nonaspirin-sensitive (n = 10) polypoid rhinosinusitis and normal controls (n = 9). Double-staining was used to phenotype inflammatory leukocytes expressing EP(1-4). Global mucosal expression of EP(1) and EP(2), but not EP(3) or EP(4), immunoreactivity was significantly elevated in aspirin-sensitive and nonaspirin-sensitive rhinosinusitis compared with controls (P < .03). This was attributable principally to elevated expression on tubulin(+) epithelial cells and Mucin 5 subtypes A and B (Muc-5AC(+)) goblet cells. In contrast, the percentages of neutrophils, mast cells, eosinophils, and T cells expressing EP(2), but not EP(1), EP(3), or EP(4), were significantly reduced (P < or = .04) in the aspirin-sensitive compared with nonaspirin-sensitive patients. The data suggest a possible role for PGE(2) in mediating epithelial repair in rhinitis and asthma. Because PGE(2) exerts a range of inhibitory actions on inflammatory leukocytes via the EP(2) receptor, its reduced expression in aspirin-sensitive rhinosinusitis may be partly responsible for the increased inflammatory infiltrate and production of cysteinyl leukotrienes that characterize aspirin-sensitive disease.