1. In the present study, we assessed the protective effects of chronic hypoxia preconditioning against heatstroke-induced injury in urethane-anaesthetized rats. Heatstroke was induced by exposing the animals to an ambient temperature of 42 degrees C. The time at which both the mean arterial pressure (MAP) and local cerebral blood flow (CBF) in the striatum began to decrease from peak levels was taken as the onset of heatstroke. Control rats were exposed to a temperature of 24 degrees C. 2. Mean arterial pressure, CBF, blood pH, PaO2, PaCO2 and survival time (the interval between onset of heatstroke and cardiac arrest) after heat stress were all lower than in control rats (in which 'survival time' was defined as > 360 min). However, blood lactate concentrations were greater in rats exposed to heat. Rats placed at high altitude (HA), when exposed to the same heat stress (42 degrees C) survived much longer (113 +/- 26 min; n = 8) than rats maintained at sea level (SL; 20 +/- 2 min; n = 8). 3. After the onset of heatstroke, blood pH and lactate concentrations were found to be significantly higher and lower, respectively, in HA rats than in SL rats. 4. Western blot assay revealed that chronic hypoxia preconditioning induced heat shock protein (HSP) 72 expression in both the kidneys and lungs. 5. Thus, it appears that the observed benefit of chronic hypoxia preconditioning is related to attenuation of tissue acidification and elevations of HSP72 expression in both kidneys and lungs during heatstroke.