BACKGROUND The novel humanized murine monoclonal antibody omalizumab prevents binding of human IgE to its high-affinity receptor. A contraindication to therapy with omalizumab is allergy to the medication or previous immediate-type hypersensitivity or anaphylaxis to omalizumab or similar medications. OBJECTIVE To determine whether a 32-year-old woman with asthma, allergic rhinitis, and idiopathic chronic urticaria and angioedema with anaphylactoid reactions to omalizumab could tolerate the medication in a desensitization protocol. METHODS Omalizumab was administered after pretreatment with nonsteroidal anti-inflammatory drugs (ibuprofen, 600 mg) while the patient was closely monitored in an intensive care unit. RESULTS Omalizumab was well tolerated using this protocol, but a serum sickness-like reaction developed that required discontinuation of the medication after the seventh dose. CONCLUSIONS Our experience suggests that some patients with anaphylactoid reactions to omalizumab can tolerate the medication when pretreated with nonsteroidal anti-inflammatory drugs but that a serum sickness-like illness may develop, requiring discontinued use of the medication.