Recently a patient with severe hypogonadotropic hypogonadism who was given luteinizing hormone-releasing hormone (Factrel) through an infusion pump developed a wheat-and-flare reaction at the sites of injection. Treatment with luteinizing hormone-releasing hormone was discontinued and the immune response was characterized. Skin testing by skin prick test was positive for luteinizing hormone-releasing hormone but negative for vehicle. Radioallergosorbent testing was performed with allergic (patient serum with an elevated serum immunoglobulin E concentration and allergic to inhalant allergens including ragweed pollen) and nonallergic controls. Radioallergosorbent testing was negative for luteinizing hormone-releasing hormone-reactive immunoglobulin E antibodies. Radioimmunoassay of serum of the allergic patient antibody to luteinizing hormone-releasing hormone was positive only for immunoglobulin E. Maximum binding occurred at a dilution of 1:10. Sera from nonallergic and unchallenged patients were negative. It is concluded that this patient developed hypersensitivity reactions caused by IgE antibody to luteinizing hormone-releasing hormone.