Localized heating of the rat sciatic nerve over a length of 5 mm for 30 min at 43 degrees C resulted in the production of heat shock protein 72 kd in every nucleated cell and in the induction of thermotolerance in the heated area. HSP-72 kd was never detected in axons. Heat treatment (30 min, 45 degrees C) of thermotolerant nerves, 24 h after pretreatment, led to histopathological changes in the nerve, similar to those in non-thermotolerant nerves after a less strong treatment, i.e. heating for 30 min at 44 degrees C. Although axons did not contain HSPs after treatment at 43 degrees C, these structures tolerated treatment at 45 degrees C. Therefore we conclude that axons in the rat sciatic nerve are relatively heat-resistant and therefore we assume that axons do not need protection by HSPs; this is in contrast to endothelial cells and Schwann cells. Axons can be damaged indirectly as a consequence of vascular damage leading to ischaemia. Development of thermotolerance of the vasculature, ensuring a sufficient blood flow in the heated area, prevents this indirect damage.