AIM: To investigate intracellular free calcium ([Ca 2+ ]i ) alterations in hypothalamus of febrile rabbits induced by endotoxin (ET), and compare with the effect of ET and IL-1? on [Ca 2+ ]i in hypothalamic neurocytes from normothermia rabbits. METHOD: The concentration of [Ca 2+ ]i was determined by using spectrofluorometer and fluorescent Ca 2+ probe fura-2 /Am. RESULTS: 1. A minute dose of ET (2 ng/mL) induced a significant rise in [Ca 2+ ]i in hypothalamic neurocytes from normothermia rabbits. The rise in [Ca 2+ ]i in hypothalamic neurocytes from febrile rabbits induced by intravenous injection of ET was also observed. 2. In hypothalamic neurocytes from normotheria rabbits, IL-1? failed to affect [Ca 2+ ]i at concentrations of 100, 500, 1 000 ng/mL, respectively. CONCLUSION:The action site of low concentration of calcium that plays a regulatory role during fever seems unlikely to be in cytosolic compartment of hypothalamic neurons. The change of [Ca 2+ ]i in hypothalamic neurocytes by ET can not be considered the direct effect of IL-1?.