Streptokinase is used worldwide as a thrombolytic agent. Allergic reactions have been observed to streptokinase; however, the immunologic mechanisms have not been described. In a case of an anaphylactic reaction to intravenously administered streptokinase during the evolution of a myocardial infarction, the patient had elevated specific IgE and IgG levels to this agent demonstrated by in vitro methods. In vivo testing demonstrated cutaneous immediate-type hypersensitivity with a typical wheal and flare reaction. Critically ill patients receive short-term treatment with streptokinase. Because of the potential danger of anaphylaxis in these patients, we provide an approach that may identify those at risk. The urgency of the requirement for immediate administration of streptokinase is such that an in vitro test cannot be used; thus, results of appropriate skin testing must be evaluated.