Hemodynamic changes of 2 patients to a 0.5-ml test-dose infusion of Fluosol-DA 20% are presented. The first patient had the following symptoms and signs approximately 2 min after receiving the test dose: normotensive bradycardia of 30 beat/min, a 35% drop in cardiac output, a 50% increase in systemic vascular resistance, and a 100% increase in pulmonary artery systolic and diastolic pressures. The patient complained of shortness of breath and diffuse pressure pain of the chest. All the signs and symptoms gradually resolved without treatment over the following 3 min. The second patient complained over mild, vague chest and abdominal pressure 2 min after the test dose. The only associated hemodynamic change was a slight increase in pulmonary artery systolic pressure. A 74% drop in the neutrophil count returned to the pretest value in 10 min. In contrast to anaphylactic or anaphylactoid-type reactions, these patients did not have urticaria and had an increase in systemic vascular resistance. Their reactions were reminiscent of those occurring during systemic complement activation. The possible mechanisms and prevention of these reactions are discussed.