Adverse reactions to drugs require that their mechanisms be elucidated, particularly when anaphylaxis is suspected. Early diagnosis can be achieved by plasma histamine measurements. Unfortunately, the short plasma half-life of histamine and the difficulties in handling the sample usually preclude this measurement, although a sensitive radioimmunologic kit is routinely available. It has been recently suggested that mast cell tryptase, a component of the mast cell granules, could provide an alternative to histamine determination. Angioedema of the face is such that the boy cannot open his eyes. This reaction was caused by an allergen exposure. Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death. Diagnosis is based on the presenting symptoms and signs after exposure to a potential allergen. The symptoms are caused by the sudden release of chemical substances, including histamine, from cells in the blood and tissues where they are stored. The release is triggered by the interaction between an allergic antibody called Immunoglobulin E (IgE) and the substance (allergen) causing the anaphylactic reaction. Anaphylaxis is a serious systemic allergic reaction that is rapid in onset and may cause death. The diagnosis of anaphylaxis during the acute event is based on the clinical presentation and a history of a recent exposure to an offending agent. There are no laboratory tests available in an emergency department or clinic setting to confirm a diagnosis of anaphylaxis in real time. Laboratory tests in serum, plasma, and possibly urine obtained during or shortly after the acute event can however help to support the clinical diagnosis of anaphylaxis. These tests can also help identify anaphylaxis in the presence of other disorders that have overlapping clinical presentations, such as severe asthma or myocardial infarction. In addition, these tests may provide evidence for anaphylaxis as a cause of death. This topic reviews the laboratory tests that can be used to support the clinical diagnosis of anaphylaxis in both adults and children. These tests are different from those that identify sensitization to histamine measurements the inciting allergen, namely measurements of allergen-specific immunoglobulin E (IgE), which are reviewed.