Purpose : Investigation of the effects of hyperthermia on the radiation response of rat lumbosacral spinal cord with respect to: (a) incidence of paralysis, (b) latency, (c) histopathology, and (d) tumor induction. Methods and Materials : Rat lumbosacral spinal cord with the cauda equina was single-dose irradiated with 15 to 32 Gy of x-rays. Hypethermia for 30 min at a spinal cord temperature of 41.1, 42.3, and 42.6 ± 0.4°C was appplied 5 to 10 min after irradiation by means of a 434 MHz microwave applicator. Animals were observed for 21 months whiel recording myelopathy and development of tumors. Results : The latent period for hind leg paralysis decreased with increasing radiation dose from 359 ± 31 days ( n = 9) after 20 Gy to 200 ± 4 days ( n = 5) after 32 Gy. Hyeprthermia enhanced the radiation response of the lumbosacral spinal cord as evidenced by shortening of the latent period for paralysis and a decrease in the biological effective dose. After 20 Gy followed by 30 min 41.1°C, latency was diminished to 214 ± 16 days ( n = 7, p < 0.001 vs. 20 Gy alone). The ED 50 was 21.1 Gy, which was diminished to values between 15 and 17 Gy if radiation was followed by hyperthermia, giving a thermal enhancement ratio between 1.24 and 1.32. Histopathological examination of the spinal cord after combined treatment of x-rays and hyperthermia showed necrosis of nerve roots.Irradiation with 16, 20, 24, and 28 Gy ( n = 77) alone led to tumor induction in 17 ± 8% of the animals (pooled data). If followed by hyperthermia ( n = 96), it was increased to 33 ± 12% ( p < 0.01). Most tumors induced by radiation and hyperthermia were sarcomas. Conclusion : First, the radiation response of rat lumbosacral spinal cord was enhanced by theat. Second, latency for paralysis was shortened in the lower dose range. Third, no difference in pathology between x-rays alone or in combination with hyperthermia. Fourth, hyperthermia did increase radiation carcinogenesis.