Three of 27 patients treated for pheochromocytoma between 1974 and 1987 presented with pheochromocytoma multisystem crisis (PMC). This unusual presentation consists of multiple organ system failure, temperature often greater than 40 degrees C, encephalopathy, and hypertension and/or hypotension. Although urgent medical therapy achieved blood pressure control in all three patients, the other manifestations of PMC progressed rapidly in spite of alpha and even beta blockade. The first patient died during attempts to localize a septic focus. The other two patients underwent urgent adrenalectomy and had postoperative improvement in their multiple organ system failure. All three tumors were large and produced markedly elevated levels of epinephrine. In conclusion (1) PMC is an unusual presentation of pheochromocytoma; (2) its manifestations include multiple organ system failure, high fever, encephalopathy, and vascular lability; (3) it may result from increased epinephrine secretion; and (4) successful treatment of PMC demands prompt diagnosis, vigorous medical preparation, and emergency tumor removal if the patient's condition continues to deteriorate.