Patients who require cardiac surgery or heart-lung transplantation may have been previously sensitized to drugs and blood products to which they may be reexposed during their current surgery. Reexposure may produce an anaphylactic reaction, a life-threatening allergic response. The presence of immunospecific immunoglobulin (Ig)E antibodies and, perhaps, certain classes of IgG antibodies may increase the risk of anaphylaxis. The substances that most commonly lead to anaphylaxis during cardiac surgery include antibiotics, blood products, colloid volume expanders, cyclosporine, and protamine. The anaphylactic potentials of several drugs commonly given in the perioperative setting are well known. Unlike oral cyclosporine for example, the intravenous form is solubilized in cremophor, a fatty-acid derivative that can directly activate the complement cascade. Protamine, whose anaphylactic potential during cardiac surgery is best understood, has been the subject of two studies in which risk of anaphylaxis was evaluated in approximately 5000 patients who received protamine reversal of systemic heparinization after cardiac surgery. This agent is a small polypeptide, derived from a fish source, with a molecular weight of approximately 5000; it is not particularly immunogenic, perhaps because it resembles human histone proteins. The risk of anaphylaxis after protamine administration is much higher among neutral protamine Hagedorn insulin-dependent diabetic patients (0.6% to 2%) than among non-neutral protamine Hagedorn insulin-dependent diabetic patients (0.06%). However, patients with pulmonary hypertension or prior exposure to protamine from previous cardiac surgery were not at an increased risk for anaphylaxis after protamine exposure. The presence of preexisting IgE antibodies has been shown to be highly predictive of the development of anaphylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)