Twelve millimeters of the thoracolumbar spinal cord of mice has been treated with a radiofrequency heating system which has been shown previously to produce localized and controllable elevation of temperature. The severity of neurological damage was assessed by measuring the reduction in the reflex leg extension of the hind legs of the mice from video-recorded images and by scoring the performance of the mice by a negative geotaxis test. The response to treatment was rapid with maximum paralysis occurring within a few days after treatment. Only minor symptoms were observed in those animals which had not developed paralysis within 2 weeks. A 40% reduction in the reflex leg extension was chosen as an end point, and the percentage of mice having reached the end point for different thermal doses was determined in groups of nine mice. The ED50 for heating for 1 h was 43.1 degrees C and for heating at 45 degrees C was 10.8 min. An increase in temperature by 1 degree C required a decrease in time by a factor of 2.25 to produce the same effect. Thermotolerance was observed 24 h after preheating at 45 degrees C for 1.9 min with a thermotolerance ratio of 1.7. The rapid response and high sensitivity of the spinal cord will have to be taken into consideration in the clinical application of hyperthermia.