Eosinophilic granulocytes (Eos) are found in great numbers both in the tissue and in the mucus of patients suffering from chronic rhinosinusitis with polyposis (ECRS). Interleukin-16 (IL-16) is known as a highly potent chemotactic and chemoattractant molecule (ED 10-11) for Eos. In an open, explorative, controlled study we examined the presence of IL-16 in mucosa tissue, mucus and serum in patients suffering from ECRS and its association to Eos activation. Tissue and nasal mucus specimen from 10 previously untreated, non allergic ECRS-patients undergoing paranasal sinus surgery and from 10 healthy non sinusitis subjects, undergoing nasal surgery because of anatomic nasal obstruction were investigated by real-time (RT-) PCR targeting human IL-16 mRNA. Haematoxylin-eosin (HE) staining and immunohistochemistry of formalin embedded tissue and mucus were applied for detection and determination of the proportion of activated Eos (aEos) and IL-16. Serum IL-16 was analyzed by enzyme-linked-immunosorbent assay (ELISA). IL-16 mRNA and IL-16 protein levels were elevated in nasal mucus, polyp tissue and in the serum of ECRS patients compared to healthy controls. There was a high proportion of aEos in ECRS patients compared to healthy subjects. Serum IL-16, IL-16 mRNA expression and IL-16 protein in mucus and tissue specimens were significantly associated with the presence of aEos in polyps of ECRS patients. Immunohistochemically IL-16 protein was mainly expressed in aEos, mast cells, lymphocytes and epithelial cells. In conclusion our data indicate that IL-16 may stimulate the migration and persistence of activated Eos in ECRS. IL-16 production in ECRS patients is not mediated by Immunglobuline-E (IgE).