To investigate whether the contrast medium iohexol alone or in combination with vascular stent-graft material induces neutrophil degranulation. Human whole blood or isolated human neutrophils were incubated with or without iohexol and vascular stent-graft material. Samples were also drawn from 5 patients undergoing diagnostic angiography using iohexol. Myeloperoxidase and lactoferrin concentrations were determined by enzyme immunoassays. Both in vitro and in the patients, iohexol induced neutrophil degranulation with considerable individual variation in dose sensitivity and timing. The in vitro effect was independent of the type of anticoagulant used (ethylenediamine tetra-acetic acid, heparin, lepirudin). Experiments using isolated neutrophils showed that degranulation was independent of complement activation or platelet-derived mediators. The dose for maximal response varied from 5 to 50 mg I/mL (10.7-107.6 mg/mL iohexol). In vitro, vascular stent-graft material alone did not induce neutrophil degranulation. As compared to iohexol alone, incubation with iohexol and vascular stent-graft material in combination substantially increased the release of myeloperoxidase. Iohexol induces neutrophil degranulation, which is greatly enhanced when combined with vascular stent-graft material. Thus, iohexol-induced neutrophil activation may contribute to an inflammatory response following stent-graft implantation. We speculate that neutrophil activation during other procedures combining catheters and iohexol (e.g., angiography) may induce inflammation, which might have detrimental effects.