Experiments were carried out to ascertain whether the levels of brain monoamines and cytokines are involved in the heatstroke-induced cerebral ischemia and neuronal damage. Heatstroke was induced by exposing anesthetized rats to a high ambient temperature of 42 degrees C; the moment at which the mean arterial pressure began to decrease from its peak level was taken as the onset of heatstroke. It was found that, during the heatstroke-induced cerebral ischemia and neuronal damage, the extracellular concentration of either dopamine, serotonin or norepinephrine were increased in the hypothalamus, the corpus striatum and other brain regions. In addition, the concentration of interleukin-1 (IL-1), IL-6 and tumor necrosis factor in both the plasma and brain was also increased during heatstroke-induced cerebral ischemia and neuronal damage. Heatstroke-induced cerebral ischemia and neuronal damage were attenuated by depletion of brain dopamine or serotonin produced by intracerebral injection of 6-hydroxydopamine or 5,7-dihydroxytryptamine, respectively. Accordingly, the survival of these heatstroke rats was increased after brain dopamine or serotonin depletion. Furthermore, heatstroke-induced cerebral ischemia, neuronal damage and monoamine accumulation were attenuated by blockade of IL-1 receptor produced by treatment with an IL-1 receptor antagonist. The survival of the heatstroke rats was also increased after induction of heat shock protein. The results suggest that marked accumulation of either dopamine, serotonin or IL-1 in brain is important for the occurrence of heatstroke-induced cerebral ischemia and neuronal damage in rats. The survival of these heatstroke rats can be increased by inhibition of IL-1 receptors or monoamine system in brain as well as by induction of heat shock protein.