Anaphylaxis is rare with opiates. A local cutaneous reaction may occur with the intravenous infusion of meperidine and should not be confused with a systemic reaction. We present a case of a local urticarial reaction associated with the intravenous infusion of meperidine in a patient with sickle cell disease. No systemic manifestations occurred and the reaction re¬ solved with the administration of an antihistamine. Localized cutaneous reactions have been reported previously with the intravenous infusion of meperidine. Rarely, a large urticarial response may occur at the infusion site resulting from direct mast cell release by the drug. A large, localized urticarial reaction may be seen with the infusion of meperidine and the patient should not be labeled as having a hypersensitivity to the drug in the absence of sys¬ temic signs or symptoms.