1. Nineteen patients with louse-borne relapsing fever were studied in Addis Abeba (altitude 2285 m).
2. Following treatment with tetracycline a febrile Jarisch—Herxheimer-like reaction developed which showed the phases described in artificially-induced endotoxin fever.
3. During the chill phase body temperature, metabolic rate and pulmonary ventilation increased. Despite alveolar hyperventilation pulmonary venous admixture was high. Cardiac output, heart rate and systemic arterial pressure increased but pulmonary arterial pressure decreased.
4. During the flush phase systemic arterial pressure fell and remained low for many hours due to reduced vascular resistance, but pulmonary arterial pressure and inflow resistance increased. Small increases in glucose, lactate, and pyruvate concentrations were prevented by inhaling oxygen.
5. Stimulation of metabolic rate, ventilation and cardiac output during the reaction was not due simply to increased body temperature, hypoxia, or acidosis but was probably attributable to spirochaetal endotoxin.
6. Limitation of pulmonary oxygen diffusion may have been responsible for the impaired pulmonary oxygen uptake in these patients.
7. During the prolonged flush phase a greatly increased cardiac output is necessary to maintain systemic arterial pressure because of the very low vascular resistance. Prevention of extracellular fluid volume depletion, early detection and prompt treatment of cardiac failure and oxygen therapy may reduce fatalities during this critical period but hydrocortisone in large doses failed to reduce the severity of the reaction.