BACKGROUND: Polyoxyethylene-sorbitan-20-monooleate (also known as polysorbate 80 and Tween 80) is a solubilizing agent ubiquitously used in nutritives, creams, ointments, lotions, and multiple medical preparations (e.g., vitamin oils, vaccines, and anticancer agents) and as an additive in tablets. Whereas its relevance as a contact allergen has declined during the past decades, it is of current relevance as a "hidden" inductor of anaphylactoid reactions. OBJECTIVE: To identify polysorbate 80 (generally believed to be an inert vehicle) as an inductor of a severe anaphylactoid reaction. METHODS: Skin prick testing, enzyme-linked immunosorbent assay, IgE immunoblotting, and flow cytometric detection of basophil activation were performed in controls and in a patient with a medical history of anaphylactic shock due to intravenous administration of a multivitamin product during pregnancy. RESULTS: Polysorbate 80 was identified as the causative agent for the anaphylactoid reaction of nonimmunologic origin in the patient. Polysorbate specific IgE antibodies were not identified in enzyme-linked immunosorbent assay and immunoblot examinations, confirming the nonimmunologic nature of the anaphylactoid reaction. CONCLUSIONS: Polysorbate 80 is a ubiquitously used solubilizing agent that can cause severe nonimmunologic anaphylactoid reactions.