Occasionally, an individual will suffer symptoms that mimic those of anaphylaxis, but which have not been caused by allergies. This is called an anaphylactoid reaction, and it occurs even though there was no previous exposure or sensitization to an allergen. Immunoglobulin E (IgE) antibodies are not involved in this condition. Instead, mast cells and basophils are directly stimulated to react without IgE stimulation.

A typical example of anaphylactoid reaction occurs when an individual shows symptoms after receiving radiographic contrast material, the dye injected into the arteries and veins before an x-ray procedure. Other drugs known to trigger an anaphylactoid reaction include polymyxin (an antibiotic) and morphine (a painkiller).

Anaphylactoid reactions respond well to the same treatment used for treating anaphylaxis. A person should immediately take epinephrine regardless of whether they believe they are having an anaphylactic or anaphylactoid reaction.