In order to assess the possible therapeutical value of interleukin-1 receptor antagonist (IL-1 ra) in the treatment of heatstroke, we evaluated the effects of heatstroke on survival time (interval between onset of heatstroke and death), systemic and striatal hemodynamic changes, and extent of striatal neuronal damage in rats treated with saline or IL-1 ra. The survival time of the heatstroke rats which received normal saline (single injection or continuous perfusion) was about 17 min. The heatstroke-induced ischemic damage to striatal neurons was due to systemic arterial hypotension, intracranial hypertension, decreased cerebral perfusion, and striatal dopamine (DA) accumulation (275%). Rats treated with a single injection of IL-1 ra (200 mu g/kg, i.v.) immediately after the onset of heatstroke survived much longer (91 min) than the controls. The prolongation of survival induced by IL-1 ra was brought about by attenuation of the arterial hypotension, intracranial hypertension, decreased cerebral perfusion, ischemic damage to striatal neurons, and striatal DA release value (204%). Furthermore, after continuous perfusion of IL-1 ra (200 mu g/kg per h, i.v.) immediately after the onset of heatstroke, the striatal DA release value of the rats was further reduced to 140% while the survival time of the rats was prolonged to up to 10 h from the onset of heatstroke. Thus, it appears that continuous i.v. perfusion of IL-1 ra is a good choice for heatstroke therapy.