The effects of interleukin-1 receptor antagonist (IL-Ira) on both local cerebral blood flow and neuronal damage of the hypothalamus, corpus striatum, cortex or thalamus were assessed in rats with heat stroke. Heat stroke was induced by exposing the urethane-anesthetized rats to a high ambient temperature (42 degrees C). Damage to the hypothalamus, corpus striatum, cortex or thalamus was scored on a scale of zero to three modified from the grading system of Pulsinelli and colleagues in which: 0 = normal, 1 = few neurons damaged, 2 = many neurons damaged, and 3 = all neurons damaged. During the onset of heat stroke, as compared to those of normothermia controls, the heat stroke rats displayed a higher value of colonic temperature or neuronal damage score, as well as a lower value of local cerebral blood flow or mean arterial blood pressure. In addition, compared to those of normothermic, control rats, the heat stroke rats had increased interleukin-1 and tumor necroting factor production in the diencephalon, brain stem and cortex. The heat stroke-induced neuronal damage and diminished local cerebral blood flow in different brain structures, as well as the systemic hypotension, were attenuated in animals pretreated with IL-1ra (200 micrograms/kg, iv) 30 min before the onset of heat stroke. The results indicate that IL-1ra attenuates the heat stroke-induced cerebral neuronal damage by reducing cerebral ischemia in rats.